Apparatus and method for catheter navigation and tip location

ABSTRACT

Devices and methods obtain and use endovascular electrograms in a number of clinical applications and settings. In one embodiment, methods for triggering analysis of an endovascular ECG waveform are based on the detection of a peak in a skin-based ECG waveform in order to determine a location of an indwelling medical device, such as a catheter. In another embodiment, the position of a catheter or other medical device within the vasculature can be determined by analysis of the energy profile of a detected P-wave. In yet other embodiments, magnetic connecting devices are used for establishing an operable connection through a sterile field.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. patent application Ser. No.13/019,939, filed Feb. 2, 2011, now U.S. Pat. No. 9,125,578, whichclaims the benefit of U.S. Provisional Patent Application No.61/282,397, filed on Feb. 2, 2010 and which is a continuation-in-part ofU.S. patent application Ser. No. 12/854,083, filed Aug. 10, 2010, nowU.S. Pat. No. 9,445,734, which is a continuation-in-part of U.S. patentapplication Ser. No. 12/815,331, filed Jun. 14, 2010, now U.S. Pat. No.9,339,206, which claims the benefit of U.S. Provisional PatentApplication No. 61/213,474, filed on Jun. 12, 2009, the disclosures ofwhich are incorporated herein by reference in their entireties.

BACKGROUND

The electrical conduction system of the heart creates specificelectrical signals, electrical energy distributions and behaviorsthereof which are indicative of specific locations in the thoraciccavity and/or of specific heart functions or conditions. When measuredendovascularly, i.e., from within blood vessels or from within theheart, certain parameters of the electrical activity of the heart can beused to identify specific locations in the cardiovascular system and/orfunctional conditions, normal or abnormal. Moreover, by locally andaccurately identifying the location and the type of condition, therapyof such conditions can be optimized and the effect of the therapymonitored in real-time.

Two types of clinical applications are typically addressed. The first isrelated to guiding endovascular devices through the cardiovascularsystem, while the second is related to the non-invasive or the minimallyinvasive remote monitoring of the electrical activity of the heart.

The guidance, positioning, and placement confirmation of endovascularcatheters are necessary in a number of clinical applications, such as,for example:

-   -   1. Central venous access, e.g., CVC, PICC, implantable ports;    -   2. Hemodialysis catheters;    -   3. Placement of pacemaker leads;    -   4. Hemodynamics monitoring catheters, e.g., Swan-Ganz and        central pressure monitoring catheters; and    -   5. Guiding guidewires and catheters into the left heart.

The location of the catheter tip is very important to the patientsafety, the duration and the success of the procedure. Today's goldenstandard for confirming the target location of the catheter tip is thechest X-ray. In addition, there are currently two types of real-timeguiding products available on the market, which try to overcome thelimitations of chest X-ray confirmation: electromagnetic and ECG-based.In hospitals where real-time guidance is used results have improved interms of reducing the number of X-rays, the procedure time, and the costof the procedure. Under real-time guidance first-time success rate hastypically increased from 75%-80% to 90%-95%. In addition, in hospitalswhere ECG guidance is used, e.g., in Italy, Belgium, Germany, chestX-ray confirmation has been eliminated for more than 90% of thepatients. Electromagnetic systems are used mostly in the United Stateswhile ECG-based systems are used mostly in Europe. Amongst other factorswhich determine the difference between the markets in the United Statesand Europe in terms of technology adoption: a) type of health carepersonnel allowed to perform procedures: nurses have more flexibility inthe United States, b) type of devices placed: PICCs are placed more andmore often in the United States, c) price sensitivity: the Europeanmarket seems to be more price sensitive, and d) the current guidingdevices are commercialized by specific manufacturers to work exclusivelywith their catheters: market penetration of the guiding systems reflectsthe market penetration of the catheter manufacturer.

It was also found that different opinions exist regarding where thetarget tip location should be: for example, lower third of the SVC orRA. Therefore guiding technologies should allow for discrimination ofthese locations. The chest X-ray, which is the current golden standarddoes not always allow for such discrimination requiring an accuracy oftypically better than 2 cm. Also, because ECG-based systems make use ofphysiological information related to the heart activity, their abilityto guide placement is accurate with respect to the anatomy. This is notthe case with electromagnetic guiding systems which measure the distancebetween the catheter tip in the vasculature and an external referenceplaced typically on the patient's chest. Because of this aspect,ECG-based systems can be used to document the final result of thecatheter placement potentially replacing the chest X-ray as the goldenstandard.

One of the most valuable diagnostic tools available, the ECG records theheart's electrical activity as waveforms. By interpreting thesewaveforms, one can identify rhythm disturbances, conductionabnormalities, and electrolyte imbalance. An ECG aids in diagnosing andmonitoring such conditions as acute coronary syndromes and pericarditis.The heart's electrical activity produces currents that radiate throughthe surrounding tissue to the skin. When electrodes are attached to theskin, they sense these electrical currents and transmit them theelectrocardiograph. Because the electrical currents from the heartradiate to the skin in many directions, electrodes are placed atdifferent locations on the skin to obtain a total picture of the heart'selectrical activity. The electrodes are then connected to anelectrocardiograph device, or computer, and record information fromdifferent perspectives, which are called leads and planes. A leadprovides a view of the heart's electrical activity between two points orpoles. A plane is a cross section of the heart which provides adifferent view of the heart's electrical activity. Currently, theinterpretation of an ECG waveform is based on identifying waveformcomponent amplitudes, analyzing and then comparing the amplitudes withcertain standards. Modifications of these amplitude components areindicative of certain conditions, e.g., the elevation of the ST segmentor of certain locations in the heart, e.g., the amplitude of the P-wave.In today's practice ECG monitors are widely used to record ECGwaveforms. More and more often applications are made available forautomatic identification of the ECG amplitude components. In certaincases tools are available for decision making support and for automaticinterpretation of ECG amplitude components with respect to underlyingheart conditions.

Remote patient monitoring is a well-established medical field. Stillremote monitoring of heart conditions is not as widely accepted as itwould be need and possible. One of the reasons is related to therelatively complicated way of acquiring signals related to the heartactivity, in particular ECG signals. Another important limiting factorof the current remote monitoring technologies is the use ofcommunications channels, like the telephone line, which are difficult tointerface with at both the patient and the physician ends.

BRIEF SUMMARY

Briefly summarized, embodiments of the present invention are directed tosystems, devices, and methods for obtaining and using endovascularelectrograms (or electrocardiograms/ECGs) in a number of clinicalapplications and settings. For example, the devices can be used to guideendovascular devices in and around the heart, e.g., guiding centralvenous access devices in the superior vena cava, right atrium, and rightventricle. Such central venous access devices may include central venouscatheters (CVC), peripherally inserted central catheters (PICC),implantable ports, hemodialysis catheters, tunneled catheters andothers.

In one aspect, one or several skin electrodes are used to obtain skinsurface ECG signals simultaneous with the acquisition of endovascular(intracavitary) electrogram (ECG) signals via the use of endovascular(intracavitary) electrodes. The simultaneous and synchronized skinsurface and endovascular ECG signals are used in one of several ways toanalyze and quantify the ECG signals as a function of the location ofthe endovascular electrode, e.g. as a function of the tip of a catheter.

In light of the above, in one embodiment the ease-of-use of theECG-based catheter navigation and tip location is enhanced. In oneaspect, for instance, skin ECG reference waveforms are simultaneouslypresented on a display with endovascular ECG waveforms measured at thetip of a catheter or other indwelling medical device. Such simultaneousacquisition and display of concurrent ECG signals allows for readyinterpretation of the endovascular ECG waveform at the tip of thecatheter. In another aspect, a skin ECG reference signal is used tosynchronize information processing algorithms applied to theendovascular ECG signal, yielding results of enhanced reliabilityconcerning changes of P-wave of the endovascular ECG signal in terms ofshape and energy.

In greater detail, in one embodiment a skin ECG signal can be used as areference and compared to an endovascular ECG signal in order to detectchanges in the endovascular ECG relative to the skin ECG.

In another embodiment, analysis of the synchronized skin and/orendovascular ECG signals can be linked to one another and/or to theperiodic electrical activity of the heart. For example, a skin ECG leadcan be used to detect the R-peak of the QRS complex of a detected skinECG waveform. Detection of the R-peak in the skin ECG waveform can beused to trigger analysis of the endovascular ECG signal in asimultaneously corresponding segments of the endovascular ECG waveform,e.g., in the segment corresponding to the P-wave. Such triggering isparticularly useful in case of arrhythmia, wherein the skin ECG waveformdoes not typically demonstrate a consistent P-wave, while theendovascular ECG waveform indeed includes a detectable P-wave segmentthat changes as a function of the location in the vasculature.

In another embodiment, a skin ECG lead can be used to monitor thepatient's heart activity at the same time an endovascular ECG lead isemployed to guide a catheter or other suitable indwelling orendovascular devices through the vasculature. In another embodiment,R-peaks detected in the skin ECG waveform are used to triggercorrelation computation and other types of signal processing on theendovascular ECG signal in order to allow for efficient noise reductionin the resultant endovascular ECG waveform.

In another aspect, a connector for establishing an operable connectionbetween a catheter in the sterile field of the patient and an ECG cableoutside of the sterile field is described, allowing for single operatorutilization of the apparatus for catheter navigation and tip locationintroduced herein.

In another aspect, algorithms are introduced that allow for mappingcertain ECG waveforms to corresponding locations in the vasculature. Inone embodiment, the algorithm analyzes directional electrical energypresent at the tip of a catheter or other endovascular device capable ofdetecting endovascular ECG signals. In another embodiment the algorithmcan map the catheter tip to a certain location in the vasculature basedon endovascular ECG signals so as to allow for catheter navigation.

In another aspect, a simplified graphical user interface is disclosed,depicting a moving graphical indicator over a heart icon so as toindicate a location of a catheter tip in the vasculature as determinedby the endovascular ECG signal. The graphical indicator can includedifferent colors and shapes, such as dots or arrows, for instance. Thecolors and shapes of the graphic indicator may change as a function ofthe tip location in the vasculature.

In another aspect, an ECG signal acquisition module is disclosed that isoperably connectable, via a suitable interface, to a mobile phone orother portable electronic device. This enables control of the ECG signalacquisition module, including ECG signal analysis, by a user of themobile phone. In another embodiment, the ECG signal acquisition modulecan be operably connected interfaced to other handheld or remotedevices.

In another aspect, a user interface is included for use in connectionwith the mobile phone or other portable device to enable ECGsignal-based guiding of endovascular devices by the mobile phone. Inanother embodiment, the user interface enables use of the mobile phoneto support analysis and archival of ECG signals, catheter information,and results of a catheter placement procedure. In another embodiment,the user interface optimizes ECG signal acquisition for remote patientmonitoring via the mobile phone or other handheld device.

There has thus been outlined, rather broadly, certain embodiments of theinvention in order that the detailed description thereof herein may bebetter understood, and in order that the present contribution to the artmay be better appreciated. There are, of course, additional embodimentsof the invention that will be described below and which will form thesubject matter of the claims appended hereto.

In this respect, before explaining at least one embodiment of theinvention in detail, it is to be understood that the embodiments are notlimited in their application to the details of construction and to thearrangements of the components set forth in the following description orillustrated in the drawings. Indeed, other embodiments in addition tothose described herein can be conceived of, practiced, and carried outin various ways. Also, it is to be understood that the phraseology andterminology employed herein, as well as the abstract, are for thepurpose of description and should not be regarded as limiting.

As such, those skilled in the art will appreciate that the conceptionupon which this disclosure is based may readily be utilized as a basisfor the designing of other structures, methods and systems for carryingout the several purposes of embodiments of the present invention. It isimportant, therefore, that the claims be regarded as including suchequivalent constructions insofar as they do not depart from the spiritand scope of this disclosure.

These and other features of embodiments of the present invention willbecome more fully apparent from the following description and appendedclaims, or may be learned by the practice of embodiments of theinvention as set forth hereinafter.

BRIEF DESCRIPTION OF DRAWINGS

A more particular description of the present disclosure will be renderedby reference to specific embodiments thereof that are illustrated in theappended drawings. It is appreciated that these drawings depict onlytypical embodiments of the invention and are therefore not to beconsidered limiting of its scope. Example embodiments of the inventionwill be described and explained with additional specificity and detailthrough the use of the accompanying drawings in which:

FIG. 1A is a block diagram that depicts an apparatus according to anembodiment of the present invention.

FIG. 1B is a block diagram of an electronic module for acquisition andprocessing of endovascular electrocardiogram according to an embodimentof the present invention.

FIG. 2 depicts an adaptor for an endovascular device according to anembodiment of the present invention.

FIG. 3 depicts a catheter steering device according to an embodiment ofthe present invention.

FIGS. 4A, 4B, 4C, and 4D depict electrode configurations that provideoptimal acquisition of endovascular electrocardiogram according tovarious embodiments of the present invention. FIG. 4A depicts a singlelead configuration, FIG. 4B depicts a modified 3-lead configuration withmonitoring and guiding capabilities, FIG. 4C depicts a telemetryconfiguration with a single grounded lead, and FIG. 4D depicts one useof ECG monitors for guiding endovascular devices.

FIG. 5 illustrates exemplary electrocardiogram signal amplitudes atdifferent locations in the central venous system.

FIG. 6 illustrates exemplary electrocardiogram signal power spectra atdifferent locations in the central venous system.

FIG. 7 illustrates exemplary electrocardiogram signal electrical energydistribution at different locations in the central venous system.

FIG. 8 depicts a graphical user interface according to an embodiment ofthe present invention.

FIG. 9 depicts a graphical user interface according to anotherembodiment of the present invention.

FIGS. 10A and 10B depict exemplary printouts for the informationdisplayed by the graphical user interface, according to an embodiment ofthe present invention.

FIG. 11 is a block diagram for a computer-based method for positioningan endovascular device in or near the heart using electrocardiogramsignals.

FIG. 12 illustrates another decision support algorithm for acomputer-based method for positioning an endovascular device in or nearthe heart using electrocardiogram signals, according to one embodiment.

FIG. 13 illustrates the cardiac conduction system of the heart.

FIG. 14 illustrates electrical signal propagation in the conductionsystem of the heart.

FIG. 15 illustrates electrical activity in the cardiovascular system dueto neuronal control system.

FIG. 16 illustrates a framework for analyzing the endovascularelectrography signals, according to an embodiment of the presentinvention.

FIG. 17 illustrates several embodiments for electrogram waveformprocessing.

FIG. 18A shows ECG leads arranged to form an Einthoven triangle.

FIGS. 18B-18F show various views of a skin ECG waveform and anendovascular ECG waveform as depicted on a graphical user interfaceaccording to one embodiment.

FIGS. 19A and 19B show various views of a skin ECG waveform and anendovascular ECG waveform as depicted on a graphical user interfaceaccording to one embodiment.

FIGS. 20A and 20F show various views of a skin ECG waveform and anendovascular ECG waveform as depicted on a graphical user interfaceaccording to one embodiment.

FIGS. 21A and 21B show various views of a skin ECG waveform and anendovascular ECG waveform as depicted on a graphical user interfaceaccording to one embodiment.

FIGS. 22A-22D show various magnetic sterile connectors according tocertain embodiments.

FIGS. 23A and 23B show various steerable sterile connectors according tocertain embodiments.

FIGS. 24A-24F show various views of a skin ECG waveform and anendovascular ECG waveform together with a heart icon to indicate aposition of an endovascular device as depicted on a graphical userinterface according to one embodiment.

FIGS. 25A and 25B show various possible depictions for use in ECGsignal-based guidance as displayed on a mobile phone according to oneembodiment.

FIG. 26 shows a depiction of the zooming of multiple ECG waveforms asdisplayed on a mobile phone according to one embodiment.

FIGS. 27A and 27B show additional ECG waveform-related depictions asdisplayed on a mobile phone according to one embodiment.

DETAILED DESCRIPTION OF SELECTED EMBODIMENTS

Reference will now be made to figures wherein like structures will beprovided with like reference designations. It is understood that thedrawings are diagrammatic and schematic representations of exemplaryembodiments of the present invention, and are neither limiting nornecessarily drawn to scale.

For clarity it is to be understood that the word “proximal” refers to adirection relatively closer to a clinician using the device to bedescribed herein, while the word “distal” refers to a directionrelatively further from the clinician. For example, the end of acatheter placed within the body of a patient is considered a distal endof the catheter, while the catheter end remaining outside the body is aproximal end of the catheter. Also, the words “including,” “has,” and“having,” as used herein, including the claims, shall have the samemeaning as the word “comprising.”

Embodiments of the present invention advantageously provide an inventiveapparatus(es), computer-based data processing algorithms and methods forobtaining and using endovascular ECGs in a number of clinicalapplications and settings. For example, once device can be used to guideendovascular devices in and around the heart, e.g., guiding centralvenous access devices in the superior vena cava, right atrium, and rightventricle. Such central venous access devices may include central venouscatheters (CVC), peripherally inserted central catheters (PICC),implantable ports, hemodialysis catheters, tunneled catheters andothers. Other devices which may benefit from guidance with the inventiveapparatus are temporary pacemaker leads placed through the centralvenous system. Catheters and guidewires used in left heart proceduresmay also benefit from the embodiments described herein by decreasing theamount of contrast and radiation required to guide these devices inposition. In another example, the apparatus can be used for minimallyinvasive monitoring and assessing heart conditions based on itselectrical activity, e.g., assessing preload in a heart cycle ormonitoring ST segments and T-waves in congestive heart failure.

In one aspect, an apparatus is described consisting of sterile adaptors,an electronic module for signal acquisition, a computer module,software, and peripheral devices and connections. In one embodiment, theelectronic module for signal acquisition can be dedicated to acquiringand processing endovascular electrical signals generated by the body(endovascular ECG), in another embodiment the electronic module can bededicated to acquiring and processing endovascular ECGs as well as skinECGs.

In one embodiment, the electronic module and the computer module can beseparate modules, in another embodiment they can be integrated in thesame module and enclosure, and yet in another embodiment they cancommunicate with each other via a wireless connection, such asBluetooth. In one embodiment, the apparatus can contain an integratedprinter, while in another embodiment the printer can be external andattached to the apparatus and the apparatus connected via network, e.g.,wireless to other devices. In yet another embodiment the apparatus canbe used for telemetry and for transmitting the endovascular electrogramsto a remote location, e.g., via a telephone line, Internet, and/orwireless phone. Any combination of embodiments mentioned above is alsopossible.

In another aspect, various configurations allow the connection ofendovascular devices, such as central venous access devices, to theelectronic module for signal acquisition and processing. In oneembodiment, the device consists of a connecting wire with two ends andspecial connectors at each end. At one end, the wire can be connected toa metal or nitinol guidewire or stylet as commonly available on themarket. At the other end, the wire can be safely connected to theelectronic module. In another embodiment, the device includes a coatedguidewire, e.g., made of nitinol or stainless steel with uncoated distaland proximal ends and cm markings. In such an embodiment, the coatedguidewire is inserted endovascularly, while the connecting wire isconnected to the proximal end of the coated guidewire. In anotherembodiment, the device includes a catheter-syringe adaptor provided withan electrical connecting wire. At one end, the electrical connectingwire is in contact with the fluid, e.g., saline flowing within thecatheter-syringe adapter. At the other end the connecting wire can beconnected to the electronic module.

In another aspect, various electrode configurations allow for theoptimal acquisition of endovascular ECGs. In one embodiment, a singlelead is used to provide information about the tip location of anendovascular device within the vasculature. In another embodiment amodified three lead configuration is used to provide simultaneous 3-leadmonitoring of the heart activity at the same time with providing tiplocation information. In another embodiment a modified single leadconfiguration plus ground is used for telemetry and transferringinformation from the tip of the catheter remotely.

In another aspect, algorithms are introduced for the analysis of the ECGwaveforms and for supporting decision making based on these waveforms.These algorithms discriminate between different locations in thevasculature and assess body functions (systemic and at specificlocations in the body), in particular heart functionality. In variousembodiments, these algorithms use time domain analysis of waveforms:morphologic, for example shape; statistic, for example behavior.

In other embodiments, the algorithms use frequency domain analysis ofwaveforms: morphologic, for example shape; statistic, for examplebehavior. In further embodiments, signal energy analysis in time andfrequency domains is also performed, morphologic and statistic. Fuzzy,statistical, and knowledge-based decision making are also contemplatedby the present embodiments as decision support tools.

In another aspect, a user interface is provided that advantageouslysimplifies interpretation of data and workflow. In one embodiment theuser interface includes simplified graphics showing the location in thevasculature and in the heart of the tip of the endovascular device inuse without showing any of the ECG waveforms. In another embodiment, theuser interface shows, in real-time, the change in location of the tip ofthe endovascular device in use.

In another aspect, several inventive methods are presented which use theapparatus described herein in clinical applications. In one embodiment,a computer-based method is provided that guides central venous catheters(CVC, PICCs, hemodialysis, implantable ports, and others) using stylets,guidewires and saline solution to the superior vena cava, inferior venacava, the right atrium, and the right ventricle. This method isadvantageously less sensitive to patients with arrhythmias than theprior art, and represents an alternative to chest X-ray confirmation oftip location of central venous catheters in most clinical cases. Inanother embodiment, a computer-based method is provided that guidescoated guidewires in the right and left heart. In another embodiment, acomputer-based method is provided that guides the placement of temporarypacemaker leads through the central venous system. In anotherembodiment, a method is provided that is minimally invasive and monitorspreload using depolarization and heart rhythms. In another embodiment, amethod is provided that is minimally invasive and monitors arrhythmiasusing P-wave analysis. In another embodiment, a method is provided thatis minimally invasive and monitors heart failure using ST segment andT-wave analysis.

In another aspect, one or several skin electrodes are used to obtainskin surface ECG signals simultaneous with the acquisition ofendovascular (intracavitary) electrogram (ECG) signals via the use ofendovascular (intracavitary) electrodes. The simultaneous andsynchronized skin surface and endovascular ECG signals are used in oneof several ways to analyze and quantify the ECG signals as a function ofthe location of the endovascular electrode, e.g. as a function of thetip of a catheter.

In light of the above, in one embodiment the ease-of-use of theECG-based catheter navigation and tip location is enhanced. In oneaspect, for instance, skin ECG reference waveforms are simultaneouslypresented on a display with endovascular ECG waveforms measured at thetip of a catheter or other indwelling medical device. Such simultaneousacquisition and display of concurrent ECG signals allows for readyinterpretation of the endovascular ECG waveform at the tip of thecatheter. In another aspect, a skin ECG reference signal is used tosynchronize information processing algorithms applied to theendovascular ECG signal, yielding results of enhanced reliabilityconcerning changes of P-wave of the endovascular ECG signal in terms ofshape and energy.

In another embodiment, analysis of the synchronized skin and/orendovascular ECG signals can be linked to one another and/or to theperiodic electrical activity of the heart. For example, a skin ECG leadcan be used to detect the R-peak of the QRS complex of a detected skinECG waveform. Detection of the R-peak in the skin ECG waveform can beused to trigger analysis of the endovascular ECG signal in asimultaneously corresponding segments of the endovascular ECG waveform,e.g., in the segment corresponding to the P-wave. Such triggering isparticularly useful in case of arrhythmia, wherein the skin ECG waveformdoes not typically demonstrate a consistent P-wave, while theendovascular ECG waveform indeed includes a detectable P-wave segmentthat changes as a function of the location in the vasculature.

In other embodiments, magnetic and steerable sterile connectors aredisclosed, as well as aspects of display and control solutions to enablea mobile phone or other handheld device to control an ECG-based systemincluding one or more of the above aspects.

FIG. 1A is a block diagram that depicts an apparatus according to anembodiment of the present invention.

The apparatus 100 can be attached through an adaptor (120) to a largevariety of commercially available and custom designed vascular accessdevices (110). Examples of such devices are: central venous catheters(CVC), peripherally inserted central catheters (PICC), implantableports, tunneled catheters, hemodialysis catheters, guiding catheters forpacemaker leads, guidewires used for coronary and other vascularinterventions, guiding catheters for coronary and other vascularinterventions, stylets, syringe needles, and others. If the vascularaccess devices is a stylet, a guidewire, or a syringe needle, itsmaterial must be sufficiently electrically conductive, e.g., stainlesssteel or nitinol. In such a case the hook or the alligator clip adaptoraccording to one embodiment should be used If the vascular access deviceis a catheter, than saline should be used to establish a conductive paththrough one of the catheter's lumens. In such a case, thesyringe-catheter adaptor according to one embodiment should be used.

The electronic module (130) receives electrical signals from the adaptorand from one or more other electrodes placed on the patient's skin(115). Alternatively, more than one adaptor can be used at the same timeto connect to more than one endovascular device in order to providedifferent electrical signals to the electronic module. The use of skinelectrodes is optional in certain device configurations. The electronicmodule processes the electrical signals and transmits them to a computermodule (140) for further processing and other functions. In oneembodiment the electronic module and the computer module can be packagedseparately, in another embodiment they can be integrated in the samepackage. In one embodiment the connection between the electronic moduleand the computer module can be hardwired, in another embodiment it canbe wireless, e.g., using Bluetooth.

The computer module processes the signals from the electronic moduleapplying algorithms (170) as described by current embodiments. Thecomputer module can also be connected to peripherals (160), e.g., aprinter or a label printer and storage devices and provides connectivityincluding wireless connectivity (150) to other computers or to theinternet. The storage device can be used to store a database ofknowledge and information regarding the application at hand. Theconnectivity interface can be used to update this database remotely withnewest relevant knowledge and information, e.g., new clinical cases, newfindings regarding the relationship between electrograms and heartconditions. The computer module supports a graphical user interface(180) optimized for the purpose of the clinical application at hand.

FIG. 1B is a block diagram of an electronic module (2) for acquisitionand processing of endovascular electrocardiogram according to anembodiment of the present invention.

The patient connector interface (10) allows for connecting electricalleads to the patient (5). Any combination of skin electrodes and/orelectrical connections to endovascular devices using the adaptorsdiscussed above can be used. In one embodiment, the amplifier (20) is afour stage amplifier with variable gain, which can amplify electricalsignals coming through the patient cable, for example, typical ofelectrocardiographic values. The analog-to-digital converter (30)converts the signals in digital format readable by the micro-processor(40). Any number and configurations of microprocessors,microcontrollers, and digital signal processors can be used to implementthe micro-processing function (45).

In one embodiment, a microcontroller is responsible for controlling theserial communication with a computer module (90) via the serialinterface (70) or via the wireless interface (80) and a digital signalprocessor (DSP) is responsible for implementing one or several of theinventive algorithms described herein. Alternatively, a single processor(46) can be used for both communication and processing.

The micro-processor (40) also receives commands from the computer module(90) and controls different elements of the electronic module, e.g., theamplifier (20) accordingly. The patient isolation block (50) decoupleselectrically the power (60) and the serial communication channel (70)from the patient interface (10) in order to ensure patient protection toelectrical shock. In one embodiment the isolation block (50) canconsists of a transformer and/or couplers, e.g. optical couplers.

FIG. 2 depicts an adaptor (200) for an endovascular device according toan embodiment of the present invention. Vascular access devices likecatheters, syringes, syringe needles, stopcocks, infusion pumps andothers connect to each other through standard connections. For example,in FIG. 2 such a standard connection between two devices is illustratedon device (201) by the luer (202) with inner diameter (203) and outerdiameter (204), and on device (250) by threaded port (251) with innerdiameter (252) and fluid opening diameter (253). The threaded port (251)and the luer (202) allow for connecting the two devices (201, 250) bythreading, attaching, coupling, etc., the port (251) into the luer(202).

The adaptor (200) has a body (220) with two ends (226, 227) with alength (225), and is made, for example, of strong biocompatible plasticmaterial with some degree of elasticity. End (227) has a shape of acone. In one embodiment, end (227) has an elastic sealing portion (228)such that end (227) can easily fit in the luer (202) of device (201) toseal the connection for fluid flow. The other end (226) is in the shapeof a standard luer, such as, for example, luer (202) of device (201).The threaded port (251) of the device (250) can be connected to end(226) of the adaptor (200). The cone piece (227) also allows aconnection to a device that does not have a luer. The standalone conepiece (270) allows a connection between two devices with differentaccessible diameters. The end (227) of adaptor (200) has a diameter(223) and fits inside the diameter (272) of the cone piece (270). Theend (271) of the cone piece (270) fits in a simple catheter end portion(261) with a diameter (262) of a typical device (260). For example,device (260) can be a catheter for an implantable port.

In one embodiment, device (201) is a syringe needle, and device (250) isa syringe. Fluid, e.g., a conductive electrolyte, flows through adaptor(200) through a central inner bore or lumen (222) having a certaindiameter, and provides a fluid path between the devices (250, 201). Aconductive metal ring (240) is attached to a portion of thesubstantially cylindrical surface of lumen (222) and, preferably,induces very little perturbations to the fluid flow. For example, themetal ring (240) may be disposed within a recessed portion of thesubstantially cylindrical surface of the lumen (222). One end (230) of aconductive wire (233) is electrically coupled to the metal ring (240);in one embodiment, the end (230) is soldered to metal ring (240). Inanother embodiment, the end (230) is captured between the surface of thelumen (222) and the metal ring (240), and the end (230) and the metalring (240) maintain good electrical contact through mechanical pressure.The wire (233) may be bare or insulated. In a preferred embodiment, themetal ring (240) is fixedly attached to the surface of lumen (222)using, for example, adhesive, an interference fit, a press fit, etc.,while in other embodiments, the metal ring (240) may be removablyattached to the surface of lumen (222), free-floating, etc.

The wire (233) passes through a channel (231), which extends from thelumen (222) to an opening in the outer surface of the body (220). Epoxy(232), or other suitable material, may be used to seal the opening ofthe channel (231), as well as to provide a strain relief for the wire(233). The metal ring (240) may be advantageously disposed adjacent tothe channel (231) to provide additional sealing. Thus, the metal ring(240), the wire (233), the channel (231) and the epoxy (232) provide asealed, electrical connection to the fluid flowing through the adaptor(200). A connector (234) may provide a standard electrical connection tothe electrography system; a non-terminated wire may also be used. In oneembodiment, the wire (233) terminates at the opening of the channel(231) and the connector (234) is attached directly to the body (222),while in another embodiment, the wire (233) extends through the openingof the channel (231) and the connecter (234) is attached to the free endof the wire (233).

In one embodiment, the substantially cylindrical surface of lumen (222)is tapered along the longitudinal direction. This taper may extend alongthe entire length of lumen (222), or restricted to a certain portionthereof. For example, the surface of lumen (222) may be cone-shaped andhave a larger diameter at the proximal end, or, alternatively, thelarger diameter may be located at the distal end.

In one example, device (201) is a syringe needle that is inserted into alumen of a catheter for an implantable port, and device (250) is asyringe. The syringe is filled with saline, which is then injected intothe catheter through the adaptor (200). Thus, the adaptor (200) becomesfilled with saline solution, and, because the conductive metal ring(240) is in contact with saline and the conductive wire (233), anelectrical connection is established between the catheter lumen and thewire (233). In this way, the electrical signal at the tip of thecatheter may be measured through the saline solution. Other electricallyconductive solutions may also be used to obtain the endovascularelectrogram using the adaptor (200). In another embodiment, the adaptor(200) may be used with infusion pumps, as well as other types of powerinjections. In an alternative embodiment, the adaptor (200) does notinclude the metal ring (240), and the electrically conductive ending(230) is in direct contact with the electrolyte.

FIG. 3 illustrates a catheter steering device according to an embodimentof the present invention. In this embodiment, the catheter (300) is atriple lumen catheter and the distal end of each of the lumens is spacedwith respect to each other. The catheter steering device can be usedwith any catheter having two or more lumens with spaced distal lumenopenings. The open end of one lumen (306) of catheter (300) is at thevery distal end of the catheter, another end or opening of a lumen (305)is spaced back from the distal end and the end or opening of the thirdlumen (307) is spaced back compared to the second end (305). Thedistance between the open end (306) and the end (307) is typically fromone to several centimeters.

Several types of catheters have multiple lumens with spaced ends, andthe inventive steering device can accommodate such catheters. Forexample, in the case of a peripherally inserted central catheter, thetypical length of a catheter is 50 to 60 centimeters and the spacingbetween the distal lumen ends (305, 306, and 307) is from one to severalcentimeters. A hemodialysis catheter with two lumens can typically be 20to 40 centimeters in length, with one to several centimeters spacingbetween the distal ends of the two lumens. A multi-lumen central venouscatheter (CVC) can typically be 15 to 25 cm in length with spacingbetween distal ends or openings of the lumens being from severalmillimeters to several centimeters.

At the proximal end, the catheter has a catheter hub (301) which splitsthe three lumens and connects each of them with a luer (302, 303, 304).The inventive catheter steering device includes a stylet (310) with ahandle (311) at the proximal end to allow for pushing, pulling, andremoval after use, and a steering member (320) which connects to thedistal end of the stylet (322) and which can be fed back into a distallumen opening of one of the other lumens, such as, for example, lumen(307). The steering member (320) returns to the proximal end of thecatheter through the catheter lumen and exits at the proximal endthrough the luer corresponding to the respective lumen (304). Sodisposed, the steering device is in the installed position. In oneembodiment, the member (320) has a handle (321) which can be used topull the member through the lumen. In another embodiment, the handle(321) is detachable from the member (320).

The member (320) may be polyurethane, silicone, PTFE, or other similarmaterials. In different embodiments, the member (320) may be any kind ofbiocompatible thread, e.g., surgical thread. In another embodiment, themember (320) is stainless steel wire. In one embodiment, the stylet isprovided pre-inserted into one of the catheter lumens, typically thecentral lumen with the most distal opening (306) with the member 320attached at the distal end of the stylet (322) and pre-inserted into thelumen (304) through the lumen opening (307). In order to steer thecatheter, the user pulls the member 320 out of the catheter whilepreventing the stylet 310 to be pulled into the catheter. Thus, thecatheter tip can be bent in a desired direction. This situation isillustrated by the bent catheter tip (350), the member (340) which waspulled back and the member (330) which is its initial position withrespect to the catheter. If the stylet (310) or the steering member(320), or both are made of any electrically conductive material, theneach or both of them can be used to measure electrical signals orendovascular electrograms at the distal tip of the catheter byconnecting their proximal ends to the endovascular electrography system.In one embodiment, the steering member (320) can be tied to the stylet(310) through the opening (307) of the catheter lumen.

In another embodiment, the stylet (310) and the steering member (320)are manufactured as a single component to form an extended steeringmember that is looped back through the opening (305) of a differentcatheter lumen. By pulling one of the two ends of the extended steeringmember coming out through luers (304) and (302), the same effect isachieved and the catheter tip can be bent in a desired direction. Inanother embodiment, in the case of a double lumen catheter, the stylet(310) can be inserted in one lumen and the steering member (320) can beinserted in the other lumen, such that the effect of bending thecatheter tip can be achieved by pulling the proximal ends. In a furtherembodiment, the steering member (320) can be inserted in the lumen (302)and through the opening (305).

FIGS. 4A, 4B, 4C, and 4D depict electrode configurations that provideoptimal acquisition of endovascular electrocardiogram according tovarious embodiments of the present invention.

FIG. 4A depicts a single lead configuration with a reference electrode(410), for example attached to the patient's skin over the right arm andwith the other electrode attached through an adaptor to an endovasculardevice (415). The reference electrode attached to the skin over theright arm is presented in this configuration for illustration purposesonly. Other locations of the reference electrode are possible dependingon the type of ECG required. The reference electrode over the right armtogether with the tip of the endovascular device used with the adaptorcan be similar to lead II of a standard ECG. In this case the ECGsobtained from the superior vena cava (401) and inferior vena cava (402)can be optimized. The reference electrode can be attached to the skin inany other location in order to simulate other leads of the standard ECG.The reference electrode can be also connected to adaptors attached toother endovascular devices in order to obtain more local informationfrom within the patient's heart (400).

FIG. 4B depicts a modified 3-lead configuration, with monitoring andguiding capabilities, with 4 electrodes. Three (3) electrodes correspondto the standard ECG electrodes: right arm (RA, 420), left arm (LA, 425),and left leg (LL, 430) used as reference. The fourth electrode isattached through an adapter to the endovascular device (C, 435). In thisconfiguration, the electronic module and the algorithm perform twofunctions simultaneously: the three standard electrodes (RA, LL, and LL)perform a monitoring function of the heart, while the C electrode (435)allow for recording the ECG at the tip of device.

FIG. 4C depicts a telemetry configuration with a single grounded lead,including the configuration illustrated in FIG. 4A and a groundreference (450). This configuration can be used to transmit ECGsremotely through a telemetry system configuration.

FIG. 4D depicts one use of ECG monitors for guiding endovasculardevices. A standard ECG monitor is used having standard inputs RA (465),LA (460), and LL (470). LA (460) is connected to the left arm and LL(470) to the left leg of the patient. The RA input (465) is connected toa switch which can be used be the clinician to switch the RA input (465)between the RA electrode and the catheter (C) electrode 475. Thus eithermonitoring or guiding of catheter placement can be achievedalternatively.

FIG. 5 illustrates exemplary electrocardiogram signal amplitudes atdifferent locations in the central venous system.

The heart (504), right atrium (501), superior vena cava (SVC) (502), andthe inferior vena cava (IVC) (503) are illustrated. Location A is in theupper SVC, location B is in the lower third of the SVC, location C is atthe caval-atrial junction, location D is in the right atrium, andlocation E is in the upper inferior vena cava.

Graph 510 illustrates an ECG waveform as a function of time at recordedat location A. The absolute amplitude of the waveforms is recorded on anamplitude scale (590). In the case of an endovascular ECG, the standardelements of the electrocardiogram are illustrated: the P-wave (560), theR-wave (570), and the T-wave (580). The amplitudes and shape at locationA recorded with a lead configuration as in FIG. 4D are similar to anelectrocardiogram recoded at the skin level with the same electrodeconfiguration.

Graph 520 illustrates an endovascular ECG depicted at location B. Theamplitude at this location is higher than the one at location A but theoverall shapes of the waveform are similar at location A and B.

Graph 530 illustrates an endovascular ECG depicted at location C. Atlocation C at the caval-atrial junction, the amplitude of the waveformis yet higher than the one at location B and the P-wave has dramaticallychanged becoming higher than the R-wave. This waveform is an indicationof the proximity of the sino-atrial node.

Graph 540 illustrates an endovascular ECG depicted at location D. Atlocation D in the right atrium, the amplitudes are similar to location Cbut the P-wave changes polarity becoming bi-polar. This is an indicationthat the measurement of the ECG occurs beyond the sino-atrial node.

Graph 550 illustrates an endovascular ECG depicted at location E. Atlocation E in the inferior vena cava, the waveform is similar to the oneat location A in terms of amplitude except the P-wave has reversepolarity. The differences in the ECG waveforms at different locationsare used by the algorithms introduced herein to discriminate between thecorresponding locations and to assess heart and blood vesselfunctionality.

FIG. 6 illustrates exemplary electrocardiogram signal power spectra atdifferent locations in the central venous system, using a spectral scale(690).

The heart (604), right atrium (601), superior vena cava (SVC) (602), andthe inferior vena cava (IVC) (603) are illustrated. Graph 610illustrates an endovascular ECG spectrum depicted at location A. Atlocation A, the spectrum (610) has the appearance of a single centralfrequency or single band (660) and with a frequency distributionspectral power and energy similar to those at skin level.

Graph 620 illustrates an endovascular ECG spectrum depicted at locationB. At location B the frequency distribution has two major bands and ahigher energy and spectral power than the one at location A.

Graph 630 illustrates an endovascular ECG spectrum at location C. Atlocation C, there are multiple (3-4) major frequencies or principalspectral components distributed over a wider range of frequencies (670).This spectral distribution is indicative of the energy distributionaround the sino-atrial node. The spectral power and signal energy haveincreased compared to location B.

Graph 640 illustrates an endovascular ECG spectrum depicted at locationD. At location D the spectrum is wider and more broadband indicative ofthe electrical activity of the right atrium.

Graph 650 illustrates an endovascular ECG spectrum depicted at locationE. The frequency spectrum at location E is similar to the one atlocation A. The differences in the spectral waveforms at differentlocations are used by the algorithms introduced herein to discriminatebetween the corresponding locations and to assess heart and blood vesselfunctionality.

FIG. 7 illustrates exemplary electrocardiogram signal electrical energydistribution at different locations in the central venous system. Theheart (704), right atrium (701), superior vena cava (SVC) (702), and theinferior vena cava (IVC) (703) are illustrated. Graphs (710, 720, 730,740, 750) depict the energy distribution at different locations (A, B,C, D and E, respectively) and the changes in time are used by thealgorithms introduced herein to discriminate between the correspondinglocations and to assess heart and blood vessel functionality.

Considering FIG. 16 for a moment, a framework for analyzing theendovascular electrography signals according to an embodiment of thepresent invention is illustrated. The heart is represented by (1600),the superior vena cava by (1601), the inferior vena cava by (1602) andthe right atrium by (1603). In this embodiment, there are three regionsof interest for placing central venous access devices: the lower thirdof the superior vena cava or SVC (1605), the caval-atrial junction orCAJ (1606), and the upper right atrium or RA (1607).

The graph (1620) illustrates the electrical energy profile as a functionof location in the heart and the graph (1640) illustrates the differentelectrography waveforms which can be obtained at different locations inthe heart. The curve (1630) illustrates the increase of electricalenergy detected in each of the regions at the tip of an endovascularcatheter advancing from the superior vena cava into the heart. In oneembodiment, the energy curve is calculated in time domain, while inanother embodiment, the energy curve is calculated in the frequencydomain using the frequency spectrum. In one embodiment, the energy iscalculated for the actual signal levels, while in another embodiment,the baseline value or other mean values are first subtracted from thesignal values before energy calculations. The signal energy or power iscalculated in time domain by summing up the squared amplitude valuesbefore and/or after baseline subtraction over a determined period oftime, e.g., a heartbeat. In the frequency domain, the signal energy orpower is calculated by summing up the squared values of the frequencycomponents. In one embodiment, the curve is calculated using the entireelectrogram, while in other embodiments, only certain segments of theelectrogram are used for the energy calculations, e.g., only the segmentcorresponding to a “P-wave” of an electrocardiogram. Such a “P-wave”segment is representative of the electrical activity of the sino-atrialnode.

Different levels of energy characterize the different locations alongthe catheter path from the SVC to the heart. These regions can bedifferentiated in terms of their electrical energy level by usingthresholds. Threshold (1631) of energy level defines the beginning ofthe lower third of the superior vena cava. The energy levels (1621)define the regions in the vasculature of low energy which are distant orfurther away from the sino-atrial node. The energy levels (1622) betweenthresholds (1631) and (1632) define the region labeled as the lowerthird of the superior vena cava (1625 and 1605). The energy levels(1623) between thresholds (1632) and (1633) define the region labeled asthe caval-atrial junction (1626 and 1606). The energy levels (1624)between thresholds (1633) and (1634) define the region labeled rightatrium (1627 and 1607).

Similarly, the shape and size of the electrogram in graph (1640)relative to a baseline (1650) can be correlated to a location in theheart. Thresholds (1631), (1632), (1633), and (1634) are determinedspecifically for the type of energy considered for calculations, e.g.the entire electrogram, the P-wave, and/or the S-T segment. Before thelower third of the SVC and corresponding to a relatively low level ofenergy (1621), the P-wave (1651) and the R-wave (1652) are similar insize and shape with a standard electrocardiogram lead II recorded at theskin level if the right arm standard ECG lead is connected to thecatheter and measuring the electrogram signal at the tip of thecatheter. In the lower third of the SVC (1605 and 1645), the energylevel of the electrogram increases, the electrogram amplitudes increaseand the P-wave (1653) increases amplitude and energy relative to theR-wave (1654) to where the P-wave amplitude and energy between half andthree quarters of the amplitude and energy of the R-wave. At thecaval-atrial junction (1606 and 1646), the energy level of theelectrogram increases further, the electrogram amplitudes continue toincrease and the P-wave (1655) increases amplitude and energy relativeto the R-wave (1656) to where the P-wave amplitude and energy are largeror equal to the amplitude and energy of the R-wave. In the right atrium(1607 and 1647), the energy level of the electrogram increases further,the electrogram amplitudes increase, the P-wave (1657) becomes bipolarand its amplitude and energy relative to the R-wave (1658) startdecreasing. These behaviors are quantified, analyzed, and used in orderto provide location information regarding the tip of the catheter.

Considering FIG. 17 for a moment, several electrogram waveformprocessing embodiments are illustrated. Graphs (1710) and (1720)illustrate a P-wave analysis embodiment. Since the P-wave corresponds toelectrical activity of the heart generated by the sino-atrial node, thechanges of the P-wave are most relevant with respect to determining theproximity of the sino-atrial node in an endovascular approach.Therefore, in order to assess proximity of the sino-atrial node andlocation in the vasculature, signal analysis methods in time andfrequency domains, as well as signal energy criteria can be applied onlyto the P-wave segment of an electrogram. In graph (1710), the segmentdesignated for the P-wave analysis (1711) starts at moment (1713) andends at moment (1714). During the period of time between the startingmoment and the ending moment of the P-wave segment, the highestamplitude detected corresponds to the P-wave peak (1712). The startingmoment (1713) of the P-wave segment analysis can be determined in anumber of ways. In one embodiment, the heart beat is calculated and theR-peak is detected as the maximum amplitude of the heartbeat. Going backfrom each R-peak a certain percentage of the heartbeat, for examplebetween 20% and 30%, determines the moment when the analysis of theP-wave starts (1713). Going back 2% to 5% of the heart beat from eachR-peak determines the end of the segment designated for the P-waveanalysis (1714). Similarly, in graph (1720), the designated segment forthe P-wave analysis (1721) starts at moment (1723) in the heart cycleand ends at moment (1724). The P-wave in this case is bipolar with apositive maximum amplitude (1722) and a negative maximum amplitude(1725) when compared to the baseline (amplitude equals zero). For theP-waveform defined between the starting point (1713 on graph 1710 and1723 on graph 1720) and the end point (1714 on graph 1710 and 1724 ongraph 1720) time-domain and frequency-domain algorithms are appliedaccording to embodiments of the present invention.

Graph (1730) illustrates the advantages of baseline subtraction prior tosignal energy computation. If the signal energy is calculated in timedomain as the sum of the squared signal amplitudes over a heartbeat,then the amplitude variations between levels (1731 and 1732) aroundbaseline (1733) may lead to a lower energy level than the signal withamplitude variations between levels (1734 and 1735) whereby the level(1734) is the baseline. The baseline value (1733) is subtracted from theamplitude values (1731 to 1732) and the baseline value (1734) issubtracted from the amplitude values (1734 to 1735). After subtractingthe baseline, the sum of squared amplitude values is calculated. Thus,this sum is proportional to the energy of signal variation around thebaseline and therefore it is more appropriate to characterize changes inthe signal values/behavior.

Graph (1740) shows a typical electrogram waveform with a P-wave (1741)and an R-wave (1742) and a distorted signal with the P-wave covered byhigh frequency noise (1744) and the R-wave saturated to a maximum value(1743). In the presence of these kinds of artifacts (1744 and 1743) itis very difficult and sometimes impossible to recover the originalsignal (1741 and 1742). Therefore, according to embodiments of thepresent invention, an algorithm is used to detect the presence ofartifacts and reduce the amount of artifacts as much as possible. If,after reducing the artifacts, the signal cannot be recovered, then thesignal is discarded for the computation of signal energy. The presenceof artifacts can be detected in time domain by a high value of thederivative and of its integral, a jump in signal energy, a jump in thevalue of the baseline or in different averages calculated from thesignal. In frequency domain, the artifacts can be detected as a jump inthe value of the DC component (frequency zero of the spectrum), as thesudden appearance of high frequency components, and in a jump of thespectral power/energy. In the frequency domain, selective filtering canbe applied and all components removed, which are not “typical” for theaverage behavior of the signal. After selective filtering, the signal isreconstructed in the time domain using an inverse Fourier transform inorder to allow for verification of the success of the selectivefiltering.

FIG. 8 depicts a graphical user interface according to an embodiment ofthe present invention.

Window (810) presents the ECG waveform in real-time as it is acquired bythe electronic module using the attached electrode configuration. Window(820) is a reference window and shows a frozen waveform used to comparewith the current window. In one embodiment, the reference waveform inwindow (820) can be obtained through the electrodes connected to theelectronic module at a reference location of the catheter and/or using areference configuration of the skin electrodes. For example, such areference waveform can be the ECG recorded using an adaptor according toan embodiment of the present invention connected to an endovasculardevice placed at the caval-atrial junction. In a different embodiment,the reference waveform in window 820 can be a typical waveform at acertain location in the vasculature or of a certain heart condition asit is recorded in a database of waveforms and as it is stored in thestorage medium of the computer system. If the electrode configurationallows for simultaneous heart monitoring and recording of electrogramsusing an endovascular device, window (830) shows one of the standard ECGleads for heart monitoring, while window (810) shows the ECG at the tipof the endovascular devices when connected to an adaptor, such as theones discussed above.

The icon (870) is a representation of the heart, and the locations Athrough E (875) illustrate different locations in the heart and vascularsystem which can be discriminated by analyzing endovascular ECGs inaccordance with the methods disclosed herein. As a location in thevasculature is identified by the algorithms, the corresponding place andletter on the icon (875) becomes highlighted or in some other way ismade visible to the user. The bars (884), (885), and (886) show signalenergy levels. The “E” bar (885) presents the amount of electricalenergy computed from the ECG frequency spectrum at the current locationof the tip of the endovascular device. The “R” bar (884) presents theamount of electrical energy computed from the ECG frequency spectrum ata reference location. The “M” bar (886) presents amount of electricalenergy computed from the ECG frequency spectrum using the monitoring ECGsignal from the skin electrodes. The window (840) depicts monitoringinformation, e.g., heart rate. Patient information (name, date ofprocedure and others) are shown in window (850). Window (860) containssystem control elements like buttons and status information, e.g.,scale, scroll speed, system parameters and system diagnostics.

FIG. 9 depicts a graphical user interface according to anotherembodiment of the present invention.

The icon (920) is a representation of the heart and the locations Athrough E (930) illustrate different locations in the heart and vascularsystem which can be discriminated by analyzing endovascular ECGs. As alocation in the vasculature is identified by the algorithms, thecorresponding place and letter on the icon (930) becomes highlighted orin some other way is made visible to the user. The bars (940), (950),and (960) show signal energy levels. The “E” bar (940) depicts theamount of electrical energy computed from the ECG frequency spectrum atthe current location of the tip of the endovascular device. The “R” bar(950) shows the amount of electrical energy computed from the ECGfrequency spectrum at a reference location. The “M” bar (960) showsamount of electrical energy computed from the ECG frequency spectrumusing the monitoring ECG signal coming from the skin electrodes. Thebutton “Print” (960) allows the user to print the informationdocumenting the case on a printer, for example on a label printer forquick attachment to the patient's chart.

FIGS. 10A and 10B depict exemplary printouts for the informationdisplayed by the graphical user interface, according to an embodiment ofthe present invention.

FIG. 10A illustrates a printout (1000) for the case of a catheter tipplacement procedure in the lower third of the SVC. The field 1010depicts the heart icon whereby the letter “B” corresponding to the lowerthird of the superior vena cava (SVC) is highlighted (1040). Field 1030depicts the reference ECG waveform recorded at the tip of the catheterat the caval-atrial junction in the proximity of the sino-atrial node.Field 1020 depicts the ECG waveform at the tip of the catheter in theposition in which it was placed at the end of the procedure. For FIG.10A, this location is in the lower third of the SVC and the ECG waveformcorresponds to this location. The patient name (1001) and the date ofprocedure (1002) are also printed.

FIG. 10B depicts a similar printout (1050) except that the finalposition at the end of the procedure is at the caval-atrial junction atlocation C (1090) on the heart icon (1060). The “SA Node” field depictsthe reference ECG waveform (1080), and the “Final Position” field (1070)shows that the catheter was placed with the tip at the sino-atrial node:the ECG waveform in final location is similar or even identical with theone in the reference location at the sino-atrial node (SA Node). It isknown that the proximity of the SA Node indicates a location at thecaval-atrial junction. These locations are sometimes consideredidentical by some clinicians.

FIG. 11 is a block diagram for a computer-based method (1100) forpositioning an endovascular device in or near the heart usingelectrocardiogram signals.

The algorithms are applied to the input signal (1102) (ECG) acquired bythe adaptor to the endovascular devices and, optionally, through skinelectrodes as well. The Error Detection Block (1105) detects at leastthree types of error conditions/exceptions, such as, for example, when adefibrillator has been applied to the patient, when a pacemaker isfiring excitation pulses and/or when a lead/electrode is off. Theseerrors/exceptions may be handled differently, and the user may beinformed about the presence of an exception and the way of handling theexception (1110).

The Pre-Processing block (1115) may amplify the signal, reduce noise,eliminate artifacts, etc. In one embodiment, rescaling the signal to thedisplay range occurs under user control and is not automatic, as withmost currently available ECG monitors. Thus, changes in the amplitude ofthe ECGs are easily noticed. A high-pass filter corrects the baselineand reduces such artifacts as respiratory artifact. Wideband noisesuppression may be achieved using a selective filter, e.g., a wavelettransform. Electromagnetic interference with other equipment and thepower grid may be suppressed by a notch filter (narrow band filter)centered at 60 Hz or 50 Hz to accommodate domestic or internationalpower supplies. High frequency noise may be suppressed with a low-passfilter, which, in one embodiment, is implemented with variable lengthaveraging, such as, for example, a running window corresponding to aheart cycle, an averaging of the ECG over several consecutive heartcycles, etc. The Adaptive Filtering block (1120) optimizes the filtercoefficients by minimizing an error signal.

The Time-Domain Pattern Recognition block (1130) identifies elements ofthe ECG waveform, their relationship(s) and their behavior(s) in time.An important aspect of the time-domain pattern recognition algorithm inblock 1130, as well as of the Frequency Domain Patter Recognition block1140, is data history. The ECGs are analyzed in real time for certainelements, and, for other elements, a data buffer with an appropriatebuffer length is maintained in the memory of the electronic and/orcomputer modules in order to allow for historic data analysis andprediction based on this analysis. In one embodiment, the data historybuffer is several seconds long allowing for the ECG signal correspondingto several heartbeats to be saved in the buffer. A double bufferingtechnique allows the waveform in one buffer to be processed while thesecond buffer continues to store signals. Thus no signal data are lostwhile the waveform in one buffer is processed. After data processing onone buffer is completed, the results are sent to the Decision SupportAlgorithms (1150) and the two buffers switch roles. The length of thebuffer accommodates the time duration of data processing in order toensure that no data are lost. A similar double buffering technique isalso applied to the data subject to Frequency Domain Pattern Recognitionblock (1140).

In the case of an endovascular ECG, elements of interest may include,but are not limited to, one or more of the following:

-   -   1. The P, Q, R, S, T, and U waves, their peaks, amplitudes and        duration;    -   2. The duration of the P-R, S-T, and T-P segments/intervals;    -   3. The elevation of the S-T segment;    -   4. The variances of the P-P and R-R intervals;    -   5. The variance of the S-T and of the R-T intervals, etc.;    -   6. The peak-to-peak values of the P-wave and of the QRS complex;    -   7. The ratio of the P-wave and R-wave amplitudes and the ratio        of the P-wave and QRS complex peak-to-peak amplitudes;    -   8. The polarity of the P-wave: single positive, single negative,        or bipolarity;    -   9. The derivative of the P-wave, QRS-complex, and T-wave;    -   10. Temporal average of the R-R interval and the heart beat;    -   11. Maximum value of the P-wave amplitude/peak and of the P-wave        peak-to-peak amplitude over a certain period of time;    -   12. Maximum value of the R-wave amplitude/peak and of the ORS        complex peak-to-peak amplitude over a certain period of time.

In the time domain, additional computations include:

-   -   13. Baseline subtraction, for example for removing of        respiratory artifacts and in order to allow for the analysis of        changes with respect to the baseline;    -   14. Waveform averaging for noise reduction;    -   15. Signal energy computation in time domain as the sum of the        squares of signal amplitudes (before and after baseline        removal);    -   16. First derivative computations for estimation of signal        changes and removal of high frequency artifacts;    -   17. Integral (sum) of the first derivative values;

In the frequency domain, additional computations include:

-   -   18. DC and quasi-DC component removal (equivalent to baseline        subtraction and removal of respiratory artifact);    -   19. Selective filtering, i.e., the removal of certain        frequencies associated with artifacts and noise, e.g., high        frequency noise, muscle artifacts, changes in signal due to        catheter and electrode handling, etc.;    -   20. Inverse Fourier transform for reconstructing the signal into        the time domain.

Several techniques may be used to derive the information listed abovefrom the ECG waveforms, including, but not limited to, one or more ofthe following:

-   -   1. “Peak detection;”    -   2. Computation of first derivatives;    -   3. Running averages along the signal in one heartbeat and along        multiple heartbeats;    -   4. Adaptive thresholding;    -   5. Auto-correlation.

The Fast Fourier Transform in block (1125) performs a Fast FourierTransform on a number of ECG samples stored in a buffer of a certainlength, e.g., 256, 512, 1024, 2048 or more data samples. The FourierTransform transforms the waveform from the time domain into thefrequency domain.

The Frequency-Domain Pattern Recognition block (1140) illustratesvarious aspects of pattern recognition performed on the ECGs in thefrequency domain, including, but not limited to, one or more of thefollowing:

-   -   1. Principal components analysis, i.e., determination of the        most significant elements of the frequency spectrum (similarly        to determining the morphological elements of the electrograms,        e.g., certain waves and segments in time domain);    -   2. Data compression in order to reduce the amount of computation        based on the principal components;    -   3. Determination of the number and morphology of the principal        components, in particular determination if the spectrum has only        one, two or multiple main frequencies (frequency bands);    -   4. Calculation of the spectral power and of the signal energy        from the frequency spectrum;    -   5. Running average along the frequency dimension over a single        spectrum in order to reduce wideband noise;    -   6. Running average along several spectra in order to filter out        artifacts;    -   7. Determination of additional morphological elements of the        spectrum, e.g., the maximum frequency, the energy contained in        the maximum frequency, the frequency histogram, i.e., what        frequencies contain how much energy, the frequency of the        highest significant maximum energy peak, etc.;    -   8. Calculation of behavior and averages over time of the        principal components and other parameters determined from the        spectral distribution, e.g., determining the maximum value of        the signal energy and of the spectral power over a certain        period of time;    -   9. Determine/estimate certain heart conditions based on the        spectral analysis. This determination/estimation is also        performed in more detailed in the decision support blocks 1150        and 1250.

Several decision support algorithms use the information provided by thetime domain pattern recognition and frequency-domain pattern recognitionalgorithms. In one embodiment, block (1150) supports placing anendovascular device in either the lower third of the SVC or at thecaval-atrial junction.

In particular, block 1150 is based on the concept of first reaching thecaval-atrial junction during catheter placement. At the caval-atrialjunction or near the sino-atrial node the P-wave and other electricalparameters reach a maximum value. At the caval-atrial junction theP-wave is unipolar. After reaching the sino-atrial node at thecaval-atrial junction, i.e., the maximum value of the P-peak amplitudeand spectral power, the catheter is pulled back several centimetersuntil the P-wave decreases to half the amplitude reached at thecaval-atrial junction. At the location where the P-wave has decreased tohalf the amplitude as the caval-atrial junction, the catheter isconsidered to be in the lower third of the superior vena cava. TheP-wave peak amplitude or peak-to-peak amplitude, as well as the spectralpower, is used to map the location in the vasculature to the ECGwaveform.

More particularly, after receiving an endovascular ECG signal associatedwith an endovascular device, the signal is processed, over a pluralityof predetermined time periods, to calculate a P-wave amplitude and aspectral power for each predetermined time period. A maximum P-waveamplitude is then determined from the plurality of P-wave amplitudes, aswell as an associated maximum spectral power from the plurality ofspectral powers. The location at which these maximum values aredetermined is associated with a predetermined location in or near theheart, such as the cava-atrial junction. The location of theendovascular device is then calculated, for each predetermined timeperiod, based on a ratio of the P-wave amplitude to the maximum P-waveamplitude and a ratio of the spectral power to the maximum spectralpower, and the location of the endovascular device is then displayed tothe user. Additionally, the polarity of the P-wave and the R-waveamplitude may also be used to determine the location of the endovasculardevice.

A single criterion or a combination of such criteria can be used tosupport decision making. In one embodiment, T1, T2, and T3 may beempirically established thresholds which are different for each patient,and the algorithm can use an adaptive loop to adjust the thresholdsbased on the current measurements. In another embodiment, thesethresholds are predetermined.

In other embodiments, the ratio between the P-peak/P amplitude or theP-wave peak-to-peak amplitude to the R-peak/R amplitude or to the QRScomplex peak-to-peak amplitude can also be used to establish locationrelative to the sino-atrial node. In one embodiment the P-peak/amplitudemust be approximately half of the R-peak/amplitude and the P-wave mustbe unipolar for the location to correspond to the lower third of theSVC. In another embodiment, the P-wave peak-to-peak must be half of theQRS peak-to-peak amplitude and the P-wave must be unipolar for thelocation to correspond to the lower third of the SVC.

As discussed above, the results of the decision support algorithms block1150 may be presented to the user, for example, by high lightening theappropriate location on the heart icon corresponding to the type of ECGidentified by the system (1160).

The decision support algorithm block 1250, depicted in FIG. 12, is basedon comparing the P-wave, R-wave and P-wave spectral power at the currentlocations with the values of these parameters determined from the skinelectrocardiograms in an equivalent lead, e.g., lead II. Thresholds T1through T6 are empirical values subject to adaptive adjustments relativeto each patient. Each of the criteria or a combination of criteria shownin FIG. 12 can be used.

Other decision algorithms can also be used, in particular related to thelevel of electrical energy as calculated from the ECG spectrum. In thecase of placing endovascular devices, one criterion may be that, at thelocation corresponding to the lower third of the SVC, the averageelectrical energy calculated from the endovascular ECG is twice as highas the average electrical energy calculated from the endovascular ECG atskin level or from a skin ECG in a corresponding lead, e.g., lead II.

Method for Placement of Central Venous Catheters

A method of placing a central venous catheter (CVC) is presented below.

-   -   1. Estimate or measure the required length of the vascular        access device (CVC) for the given patient.    -   2. If using saline and adaptor (200), go to step 11; if not,        proceed as follows. Insert a guidewire into the CVC and flush        align the guidewire tip and the catheter tip. Measure the length        of the guidewire outside the CVC. This measurement is necessary        in order to be able to realign the tip of the catheter and of        the guidewire after inserting the guidewire in the vasculature.        After taking the measurement, for example with sterile measuring        tape or with surgical thread, remove the guidewire from the CVC.    -   3. Gain vascular access and insert the guidewire for the        estimated required length.    -   4. Insert the CVC over the wire such as to leave outside the CVC        the length of the guidewire measured at step 1. Thus the CVC        inserted over the wire and the guidewire tips are flush-aligned.    -   5. Connect a sterile electrical adaptor to the guidewire per the        instructions for use.    -   6. Connect the other end of the sterile electrical adapter to        the ECG cable of the electrography system.    -   7. Check that the display of the electrography system indicates        desired position of the catheter tip per the instructions for        use of the electrography system: in the lower third of the SVC,        at the caval atrial junction or in the right atrium. Typically,        the location of the tip of the catheter will be identifiable        through the specific shape of the P-wave and of the P-wave        relative to the R-wave of the electrogram and/or by the energy        levels and thresholds.    -   8. Adjust the position of the guidewire and CVC by pulling        and/or pushing them together as not to change the flush        alignment until the ECG waveform on the screen indicates that        the desired position has been reached. Correlate the actual        inserted length with the estimated length.    -   9. After the position has been reached, disconnect the        electrical adaptor and remove the guidewire.    -   10. Secure the CVC in location.    -   11. Continue here if saline and adaptor (200) are used.    -   12. Gain vascular access and introduce the CVC over the        guidewire as currently specified by the existing protocols.    -   13. Remove the guidewire    -   14. Attach the sterile adaptor (200) to the CVC.    -   15. Attach the electrical connection (234) of the adaptor (200)        to the ECG cable of the electrography system.    -   16. Fill a syringe with saline and connect it to the other end        of the adaptor (200). Flush the catheter lumen with saline as to        create a conductive saline column all way through the catheter        tip.    -   17. Check that the ECG waveform shown on the display of the        electrography system indicates desired position of the catheter        tip per the instructions for use of the electrography system: in        the lower third of the SVC, at the caval atrial junction or in        the right atrium. Typically, the location of the tip of the        catheter will be identifiable through the specific shape of the        P-wave and of the P-wave relative to the R-wave of the        electrogram and/or by energy levels and thresholds.    -   18. Adjust the position of the CVC by pulling and/or pushing        until the ECG waveform on the screen indicates that the desired        position has been reached. Correlate the actual length with the        estimated length.    -   19. After the desired position has been reached remove the        syringe and the adaptor (200).    -   20. Secure the catheter.        Method for Placement of Implantable Ports

A method of placing the catheter piece of an implantable port is similarto the method for placing a CVC. The adaptor (200) should be connectedto the catheter of the implantable port, and the syringe with salinemust be connected to the other end of the universal adaptor. A differentelectrical adaptor should be connected to a syringe needle placed in thecatheter of the implantable port. After reaching the desire position,the catheter should be connected to the implantable port.

Method for Placement of Peripherally Inserted Central Catheters Open andClosed Ended

Both open-ended and closed-ended peripherally inserted central catheters(PICC) can be placed as described herein, and the method of PICCplacement is similar to the one of placing CVCs. The inventive steeringmechanism described herein can be used to bend the tip of the PICC incase the catheter fails to advance in the desired direction.

Method for Placement of Hemodialysis Catheters

A method for placing hemodialysis catheters is similar to the methodintroduced herein for placing CVCs. The inventive steering mechanismdescribed herein can be used to bend the tip of the hemodialysiscatheter in case the catheter fails to advance in the desired direction.Two different guidewires with adaptors (220) can be used for each of thelumens of the hemodialysis catheter as to guide placement of one lumeninto the right atrium and of the other lumen at the caval atrialjunction using the electrography system. Each of the lumens of thehemodialysis catheter can be placed independently in sequence or at thesame time by connecting the adaptors (220) of each of the lumens withdifferent electrodes of the ECG cable of the electrograph system.

Method for Placing Central Venous Access Devices in Patients withArrhythmias

Traditionally, patients with arrhythmias have been excluded fromprocedures of guiding central venous lines placement using theendovascular ECG method because of the lack of visible changes in theshape of the P-wave. The energy criteria for the P-wave analysisdescribed herein can be used to guide the placement of central venousaccess devices in patients with arrhythmias. In arrhythmia patients, theelectrical signals generated by the sino-atrial node have a certaindegree of randomness, such that they are not synchronized in order toproduce a consistent P-wave. Nevertheless, as previous studies haveshown, the electrical activity of the sino-atrial node exists andgenerates electrical energy of intensities typical to the proximity ofthe sino-atrial node. In one embodiment, the algorithm uses the energyas measured from the endovascular electrogram in order to map certainlocation in the vasculature. As such, this algorithm can be used toguide placement in patients with arrhythmias when only the electricalenergy is indicative of location but not the shape of the P-wave.

Method for Monitoring Tip Location and Certain Aspects of the ElectricalActivity of the Heart

Certain aspects of the electrical activity of the heart can be monitoredcontinuously or intermittently using the devices introduced herein.Either an electrical adaptor or adaptor (200) connected to theelectrography system can be used for monitoring. The electrical adaptorcan be connected to any stylet or other conductive member introduced inany venous access device or in any arterial device. Adapter (200) canalso be connected to any venous or arterial line as long as the infusionof a conductive solution, e.g., saline is possible. Adapter (200) canalso be used when electrically conductive fluids are inserted in thebody using an infusion pump. Monitoring the tip location and/or certainaspects of the electrical activity of the heart can be performed in anumber of clinical situations.

-   -   1. Adaptor (200) can be attached to a number of central venous        devices post insertion, e.g., at bedside and/or in home care        situations: PICCs, CVC, hemodialysis catheters. By connecting        the adapter to such a catheter and to an electrography system        according to an embodiment of the present invention and by        injecting saline into the catheter, the location of the tip of        the catheter can be confirmed and/or certain electrically        activity of the heart can be monitored during the time the        adapter is connected by using methods similar to those        introduced above in embodiments of the present invention.    -   2. Adaptor (200) can be connected to an arterial line between        the arterial line and the other devices connected to the        arterial line. The blood present in the arterial line and in the        universal adaptor ensures the electrical connection between the        blood and the electrography system. Thus the electrical activity        of the heart can be continuously monitored. This is particularly        important in the case of monitoring the preload changes which        translate in changes of the electrical energy of the heart        during the S-T segment of the ECG waveform.    -   3. Monitoring of the tip location and of the electrical activity        of the heart can also be achieved by using the electrography        system and connecting the adaptor (200) between a central venous        line and a pressure measuring system while performing central        venous pressure measurements.    -   4. In the case of an implanted port, a needle can be inserted        into the port chamber and the catheter can be flushed with        saline using a syringe filled with saline. An electrical adaptor        can be attached to the needle and to the electrography system.        The detected electrogram signal will contain information from        the skin level where the needle is in contact with the skin and        from the tip of the catheter through the injected saline column.        Since the impedance of the path to the catheter tip is lower        than the one to the skin, the detected signal contains both        components, i.e., at the skin level and at the tip of the        catheter. By subtracting the skin level signal, the signal at        the tip of the catheter can be estimated and thus the tip        position and certain electrical activity of the heart according        to the algorithms described in embodiments of the present        invention.

FIG. 13 illustrates the cardiac conduction system of the heart, whileFIG. 14 illustrates electrical signal propagation in the conductionsystem of the heart.

These figures illustrate the conductive mechanism of the heart, whichexplains why the electrical energy distribution within the heart asmeasured is indicative of specific locations within the heart.Accordingly, local electrical signals, behaviors and energyconcentrations can be measured and locations within the heart and bloodvessel can be determined more accurately; local heart conditions canalso be described more accurately.

The conduction system of the heart begins with the heart's dominantpacemaker, the sino-atrial node (1310). The intrinsic rate of the SAnode is 60 to 100 beats/minute. When an impulse leaves the SA node, ittravels through the atria along the Bachmann's bundle (1350) and theinter-nodal pathways, on its way to the atro-ventricular (AV) node(1320) and ventricles. After the impulse passes through the AV node, ittravels to the ventricles, first down to the bundle of His (1330) thenalong the bundle branches and finally down to the Purkinje fibers(1340). Pacemaker cells in the junctional tissue and Purkinje fibers onthe ventricles normally remain dormant because they receive impulsesfrom the SA node. They initiate an impulse only they do not receive onefrom the SA node. The intrinsic rate of the AV junction is 40 to 60beats/minute, the intrinsic rate of the ventricles 20 to 40beats/minute. The different propagation speeds of the electricalimpulses are shown in FIG. 14. From the SA node (1410) the impulsespropagate through the atrial muscle (1420) and through the ventricularmuscle (1460) at app. 0.5 ms, through the bundle branches (1440) and(1450) at app. 2 m/sec, through the Purkinje fibers (1470) at app 4 m/sand through the AV node (1430) at app. 0.05 m/s.

The electrical signals and the electrical energy distribution areadvantageously used to identify the proximity of the sino-atrial nodeand right atrial electrical activity even in the cases of arrhythmia,i.e., in the absence of a coherent P-wave measured by standard skinelectrocardiogram. While in some cases of arrhythmia random electricalsignal generated in the right atrium is not coherent enough to propagatethrough the body to the skin, the electrical energy is still present inthe right atrium and can be detected by local endovascular measurementsas a non-coherent P-wave, i.e., as significant electrical activity inthe P-segment of the ECG waveform. Energy measurements are also lesssensitive to some local abnormalities in impulse conduction: alteredautomaticity (arrhythmias), retrograde conduction of impulses, reentryabnormalities.

The electrical signals and the electrical energy distribution are alsoadvantageously used to quantify heart functionality, e.g., preload whichis related to the depolarization and extension of the heart muscle.

The electrical signals and the electrical energy distribution are alsoadvantageously used to guide guidewires and guiding catheters throughthe aorta into the left heart. This method is useful in simplifying theaccess to the left atrium and to the coronary arteries and in reducingthe amount of contrast and radiation needed to guide endovasculardevices to those locations. In a different application, the inventiveapparatus can also be used to guide catheters, e.g. Swan-Ganz throughthe right ventricle into the pulmonary artery. Other endovasculardevices can be guided and be used to measure endovascular electricalactivity in other locations of the cardiovascular system which areidentifiable by the cardiograms measured with the new apparatusintroduced in embodiments of the present invention.

FIG. 15 illustrates electrical activity in the cardiovascular system dueto neuronal control system. Several paths of conduction are related tothe mechanism of control of heart (1530) and blood vessel (1520)activity: receptors (1510), e.g., pressure receptors transmitinformation related to the state of the blood vessels and to the stateof the heart to the nervous system through the Medullary centers (1500).The hypothalamus (1540) and the higher centers (1550) are involved inprocessing and reacting to the information received from thesensors/receptors. In turn they send impulses (1560) back to bloodvessels and the heart. By measuring electrical activity related to thecontrol system, information regarding heart conditions can be obtainedwhich could not have been obtained previously.

FIG. 18A illustrates the Einthoven ECG triangle and the namingconvention for the ECG leads as they are used herein in connection withvarious embodiments. In order to obtain ECG signals from the patient,typically, one electrode is placed on the right arm (RA), one on theleft arm (LA) and one is used as reference on the left leg (LL). Thedirection in which the P-wave changes most is shown by the arrow (2200).Therefore, when using endovascular ECG for catheter navigation and tiplocation, the electrode corresponding to the right arm (RA) is operablyconnected to the proximal end of the vascular access device (110) (FIG.1A), such as a catheter, in one embodiment. In this way, an ECG waveformdetected with respect to the distal end of the catheter, e.g., via anelectrode disposed on the catheter, can be considered as detected byLead II of the Einthoven triangle. Thus, when the catheter is advancedthrough the vasculature, Lead II will show most significant changes ofthe P-wave and therefore is best suited to detect the proximity of thesino-atrial node. The sino-atrial node is located at the caval-atrialjunction and is responsible for generating the P-wave (indicative of theright-atrial electrical activity). The waveform corresponding to LeadIII in the Einthoven triangle remains relatively unchanged as thecatheter navigates through the vasculature in one embodiment if the RAelectrode is operably connected to the catheter. Therefore, Lead III isused in an embodiment of the present invention as a reference lead whichserves multiple purposes, as described herein. In one embodiment, theapparatus introduced herein displays simultaneously ECG signal-basedwaveforms for Lead II, also referred to herein as the endovascular ECGlead, (for catheter navigation and tip positioning) and for Lead III,also referred to herein as the skin ECG lead, (as a reference waveform).

Reference is again made to FIG. 5, which illustrates the mapping ofdifferent endovascular ECG waveforms to the corresponding locations inthe vasculature and in the heart, according to one embodiment. Indetail, Location A corresponds to the upper superior vena cava (SVC),Location B corresponds to the lower ⅓ A of the SVC, Location Ccorresponds to the caval-atrial junction, Location D corresponds to theright atrium, and Location E corresponds to the lower atrium and/or tothe inferior vena cava.

FIG. 18B illustrates the endovascular (Lead II) ECG waveform (2215)obtained with a device disclosed herein, such as an ECGsensor-containing catheter, as measured at Location A in FIG. 5. Theskin ECG waveform (2210) represents a skin reference ECG lead equivalentwith Lead III. A reference P-R complex is illustrated by (2280). Thetypical P-R complex at Location A is illustrated by (2250). While theP-wave changes dramatically on Lead II according to movement of thecatheter and its ECG sensor within the vasculature, as seen in the P-Rcomplex (2250) for instance, the P-wave remains substantially constanton Lead III used as a reference (2280).

In one embodiment, waveforms from two ECG leads (e.g., Lead II and IIIin FIG. 18B) are simultaneously depicted on a display of an apparatus,such as a catheter placement system for example, as illustrated in FIGS.18B-18F. In another embodiment, three leads (Lead I, II, and III of FIG.18A) may be displayed at the same time as shown in FIG. 20F.

By using the method, apparatus, and ECG electrode configurationintroduced herein, it is possible in one embodiment to monitor thepatient condition, e.g., the patient's heart rate using the skinreference lead (Lead III) while at the same time guiding the catheterplacement using endovascular Lead II.

FIG. 18C illustrates the endovascular ECG waveform (2220) obtained withthe device disclosed herein as measured at Location B in FIG. 5. Theskin ECG waveform (2210) represents a skin reference lead equivalentwith Lead III. A reference P-R complex is illustrated by (2280). Thetypical P-R complex at Location B is illustrated by (2255). As before,while the P-wave changes dramatically in the P-R complex (2250) on LeadII corresponding to the tip of the catheter, the P-wave remains quiteconstant on Lead III used as a reference (2280).

FIG. 18D illustrates the endovascular ECG waveform (2225) obtained withthe device disclosed in an embodiment of the present invention atLocation C in FIG. 5. The ECG waveform (2210) represents a skinreference lead equivalent with Lead III. A reference P-R complex isillustrated by (2280). The typical P-R complex at Location C isillustrated by (2260). While the P-wave changes dramatically in the P-Rcomplex (2260) on Lead II corresponding to the tip of the catheter, theP-wave remains quite constant on Lead III used as a reference (2280).

FIG. 18E illustrates the endovascular ECG waveform (2230) obtained withthe device disclosed in an embodiment of the present invention atLocation D in FIG. 5. The ECG waveform (2210) represents a skinreference lead equivalent with Lead III. A reference P-R complex isillustrated by (2280). The typical P-R complex at Location D isillustrated by (2265). While the P-wave changes dramatically in the P-Rcomplex (2265) on Lead II corresponding to the tip of the catheter(265), the P-wave remains quite constant on Lead III used as a reference(2280).

FIG. 18F illustrates the endovascular ECG waveform (2240) obtained withthe device disclosed in an embodiment of the present invention atLocation E in FIG. 5. The ECG waveform (2210) represents a skinreference lead equivalent with Lead III. A reference P-R complex isillustrated by (2280). The typical P-R complex at Location E isillustrated by (2270). While the P-wave changes dramatically in the P-Rcomplex (2270) on Lead II corresponding to the tip of the catheter, theP-wave remains quite constant on Lead III used as a reference (2280).

FIG. 19A illustrates the ability of the apparatus introduced herein,e.g., a catheter placement system, to show several display windows atthe same time on the screen thereof. One, two, or more display windowscan be included. Each of the display windows (3310 and 3320) can displayone to three ECG waveforms (leads I, II, and III) in any combination, inreal-time acquisition, in playback, or frozen modes. In one embodiment,one display window (3310) is used to show real-time ECG waveforms(catheter guiding, or endovascular, lead II and skin reference lead III)and another display window (320) is used to show frozen ECG waveforms(catheter guiding lead II and skin reference lead III). Thus, the usercan compare the changes in the catheter guiding lead and in particularin the P-R complex at two different catheter tip locations: at the tiplocation frozen in display window (2320) and at the current (real-time)tip location displayed in window (2310).

The above multi-window comparison enables the use of the followingcatheter placement method, according to one embodiment: first advancethe catheter in the atrium until the P-wave reaches its maximumamplitude as seen in window (2320) (FIG. 19B) and then pull back thecatheter to a location where the P-wave is half the size of its maximumamplitude. Such a location where the amplitude of the P-wave is half thesize of its maximum amplitude is indicative of the lower third of thesuperior vena cava (Location B in FIG. 5).

FIG. 20A illustrates how the skin reference lead can be used to analyzethe P-wave segment of the catheter guiding lead (Lead II), according toone embodiment. The P-wave segment, in which is found the P-wave itself,is characterized by the fact that it immediately precedes the QRScomplex of the same heartbeat. The P-wave segment of a heart beat alsofollows the T-wave of the previous beat. In order to detect the P-wavesegment, an algorithm can be applied including detection of the R-peakof the QRS complex. The algorithm in one embodiment includes thefollowing steps:

-   -   Detect R-peak.    -   Compute R-R interval.    -   Assume that a certain percentage of the R-R interval prior to        the R-peak is the interval in which the P-wave occurs. This        interval where the P-wave occurs is defined as the P-wave        segment.    -   Detect the P-peak in the P-wave segment, its amplitude and        polarity.    -   Apply processing, analysis and decision making algorithms as        illustrated in FIGS. 11 and 12.

In one embodiment, in order to apply the algorithm described above, theR-peak and the R-R interval can be detected on endovascular Lead II,i.e., on the same ECG lead which is used for guidance. In anotherembodiment, the R-peak and the R-R interval can be detected using LeadIII (the skin reference lead). In particular, the R-peak detection onLead III (2410) in FIG. 20A can be used to trigger the analysis of anysegment of the ECG waveform on Lead II including the analysis of theP-wave segment (2420) in FIG. 20A. It is also possible, if the signalquality of Lead II allows, to use the R-peak (2430) detected on lead IIitself to trigger processing of the Lead II waveform. In otherembodiments, other leads can be used to implement triggering on adifferent lead than the one used for catheter navigation and tippositioning. For example, Lead I can optionally be used for catheternavigation and tip positioning. The apparatus according to oneembodiment allows also the use of Lead I for catheter navigation and tippositioning, though Lead II is suitable in many clinical settings. Notethat in one embodiment the above triggering can occur for peaks on awaveform detected by the same lead. Also, a peak detected on Lead II canbe used to trigger analysis of Lead I, in one embodiment. Thus, theseand other variations are contemplated.

Triggering analysis on one ECG lead that is different than the ECG leadused for catheter navigation and positioning as introduced herein isuseful in many practical situations regardless of which ECG lead is usedfor triggering the analysis and which ECG lead is used for catheternavigation and positioning. As will be seen in FIGS. 20B-20E andespecially in FIG. 20E, triggering on a stable, noiseless lead, e.g.,Lead III improves the ability to process different segments of otherleads, e.g., endovascular Lead II used for catheter navigation andpositioning in cases where the Lead II ECG signal includes a greaterthan desired amount of signal noise. Noisy Lead II ECG signals appearquite frequently in practical settings because of the manual handling ofthe Lead II connection by the user. Other situations can benefit fromthe trigger concept introduced herein, as will be seen below.

FIG. 20B illustrates how the R-peak detected on reference skin Lead III(2410) and the corresponding R-R interval trigger the analysis of thePQRS segment (2430) on the navigation Lead II. As described herein, theP-wave segment and the QRS complex of the ECG Lead II can be analyzedseparately or in relationship to each other in order to predict thelocation of the catheter tip in the vasculature. In the case shown inFIG. 20B, the P-wave has a large positive amplitude which is equal tothe R-amplitude and is also bipolar (has a negative first segment). Insuch a case, the detection of the R-peak on the Lead II itself is verydifficult if not impossible through the use of algorithms. Triggeringthe ECG waveform analysis of Lead II (2430) based on detection of theR-peak detected on the reference Lead III (2410), as introduced herein,allows for detection and processing of the changes of the P-wave segmentcharacteristics of the catheter tip location. Such algorithmic ECGwaveform analysis of Lead II would otherwise be difficult in the caseshown in FIG. 20B because of the difficulty of clearly detecting theR-peak on this lead.

FIG. 20C illustrates how triggering on the R-peak of one lead, forexample the R-peak of Lead III (2410) can be used to trigger theanalysis of the P-wave segment on catheter navigation Lead II (2440) inthe case of a patient with arrhythmias. Typically, the P-wave segment isnot present in the skin ECG lead in patients with arrhythmias, as seenin FIGS. 20C and 20D. However, the catheter navigation and tippositioning lead, e.g., Lead II, can detect a relatively higher level ofelectrical activity in the P-wave segment as the catheter approaches thesino-atrial node and the caval-atrial junction. The level of electricalactivity (energy) in the P-wave segment increases further as thecatheter tip passes the sino-atrial node and enters the right atrium.Since the highest level of this increased electrical activity on theP-wave segment of navigation Lead II cannot be predicted, e.g., theP-wave amplitude could be higher than that of the R-wave on the Lead II,triggering the analysis of the said P-wave segment on the R-peak of askin ECG lead provides a suitable solution to P-wave detection andsubsequent catheter tip location and positioning.

FIG. 20D illustrates the lack of P-wave in the case of an arrhythmiapatient on both ECG leads II and III. In FIG. 20D, lead II is connectedto a skin electrode on the right arm of the patient and lead III to askin electrode on the left arm of the patient. The R-peak on lead III(2410) is depicted in this figure and the corresponding segment showingthe absence of a discernible P-wave on lead II is shown as (2450).

FIG. 20E illustrates the situation in which the catheter navigationlead, e.g., Lead II, is noisy or unstable and the detection of theR-peak and of the corresponding P-wave is thus difficult. In this case,as before, detecting the R-peak (2410) on a stable reference lead, e.g.,the skin Lead III, preserves the ability via the above-describedtriggering, to find and analyze the P-wave segment (2460) on the noisiercatheter navigation lead.

FIG. 20F illustrates another embodiment, wherein two leads (in thisexample Leads I and II—see FIG. 18A) are used to detect simultaneous,corresponding ECG waveforms (2470) and (2475) and triangulate, togetherwith an additional, simultaneous ECG waveform (2480) of the referencelead (Lead III), the location of the catheter tip. In particular, asubstantially accurate location of the catheter tip can be determined bylooking at Leads I and II at the same time and use their correlation (orlack thereof) to reduce noise and more accurately determine the changesof the P-segment, of the QRS segment, and the relative changes betweenthe P-wave and the QRS complex.

FIGS. 21A and 21B illustrate details regarding an algorithm to use theP-wave segment and/or its relationship with the QRS complex for catheternavigation and tip location in the case of arrhythmia, according to oneembodiment.

Specifically, FIG. 21A illustrates the ECG waveforms for two skin ECGleads (using skin electrodes). In FIG. 21A, Lead III with itscorresponding R-peak (2510) is detected using the skin left armelectrode and Lead II showing the lack of the P-wave (2520) is detectedusing the skin right arm electrode, both being compared with the skinleft leg electrode, in one embodiment. Previously, patients showingthese typical arrhythmia ECG waveforms were not considered as candidatesfor using the ECG-based method for catheter navigation and tip location.It was believed that, because the P-wave is not present at the skinlevel, the ECG method cannot be used to determine catheter tip locationat the caval-atrial junction. FIG. 21A thus illustrates a situationwhere the R-peak of the skin reference lead (2510) can be used tocompute the characteristics and the energy of the P-segment (P-wave) onthe navigation lead at locations where the P-wave is not present.

In greater detail, FIG. 21B illustrates ECG waveforms as obtained withthe apparatus described in connection with FIGS. 20A-20E and show that,with the apparatus and method described herein, even arrhythmia patientscan be treated using ECG-based catheter navigation and tip location. Dueto the processing algorithms described in FIGS. 11 and 12, the ECGsignal obtained from the tip of the catheter on Lead II is more accurateand less noisy when compared to prior art. Thus, changes in the P-wavesegment (2530) become visible when the catheter tip is in the proximityof the sino-atrial node. They correspond, as justified by physiology, toa random electrical activity of the right atrium. This random electricalactivity and its changes can be detected with the apparatus introducedherein as illustrated by the P-wave segment (2530). This randomelectrical activity typically cancels out once reaching the skin and theLead III and thus is difficult or impossible to detect by prior art ECGmethods.

Sometimes the above random electrical activity of the right atrium isalso very weak and an apparatus such as the one introduced herein isneeded to detect it even at the tip of the catheter. By observing and/oranalyzing the changes of the P-wave segment on the catheter navigationlead, the tip location of the catheter can be mapped, for example, tolocations in the superior vena cava (weak, low energy or no P-wave), tolocations at the caval atrial junction and to locations in the rightatrium. FIG. 21B illustrates how the R-peak on the reference lead (e.g.,skin Lead III) can trigger the analysis of the corresponding P-wave(P-segment) on the navigation lead (e.g., endovascular Lead II) atlocations where a P-wave segment (2530) is present.

In addition to those described in FIGS. 11 and 12, it is appreciatedthat other decision algorithms can be used, such as those related to thelevel of electrical energy as calculated from the electrogram spectrum,in placing a catheter or other endovascular devices. For instance, onecriterion specifies that at the location corresponding to the lowerthird of the SVC, the average electrical energy calculated from theendovascular electrogram is twice as high as the average electricalenergy calculated from the endovascular electrogram at skin level, e.g.,from a skin electrocardiogram in a corresponding lead, e.g., Lead III.

In addition to the algorithms disclosed above in connection with FIGS.11 and 12, the concept of directional energy and of decision makingbased thereon are introduced herein. As seen, for example, in FIGS. 18Bat (2250) and 18C at (2255), the P-wave is uni-polar, i.e., has a singlepolarity, the polarity being positive. In comparison, FIGS. 18D at(2260) and 18E at (2265) illustrate a bi-polar P-wave, i.e., a P-wavewhich has both a negative and a positive component. FIG. 18F illustratesa P-wave segment at (2270) with a uni-polar P-wave segment but ofpolarity reversed compared to that of the P-wave segment shown in FIGS.18B and 18C.

The above change of polarity in the P-wave segment is due to thelocation of the catheter tip relative to the sino-atrial node and of thelocations of the skin electrodes according to the Einthoven triangle(FIG. 18A). In the cases illustrated herein, as the catheter navigatesfrom the superior vena cava through the caval-atrial junction, throughthe right atrium and into the inferior vena cava, the polarity of theP-wave segment changes correspondingly.

According to one embodiment and in light of the above, catheter tiplocation can be determined by the following: a positive energy value anda negative energy value are determined for a detected P-wave by theapparatus described herein, such as a catheter placement system. Thepositive P-wave energy value is determined according to the energycomputation algorithms described herein, but only for positive values ofthe P-wave (i.e., values above the ECG baseline). Correspondingly, thenegative P-wave energy value is determined according to the energycomputation algorithms described herein, but only for negative values ofthe P-wave (i.e., values below the ECG baseline). These energy values(positive and negative) determined according to the present embodimentare also referred to herein as “directional energy” values because theyare related to the direction and location of the catheter tip at whichpoint the P-wave is being detected via an appropriate sensor in operableconnection with a corresponding ECG lead, such as the endovascular LeadII discussed above.

The P-wave directional energy described above can be used to guidenavigation of a catheter and for locating a tip thereof, according toone embodiment. Particularly, in one embodiment a standard Einthovenelectrode configuration, with the right arm electrode detectingendovascular ECG signals at the catheter tip (as described above inconnection with FIGS. 20A-20E) is considered. Note that other electrodeconfigurations are also possible. If the P-wave energy is substantiallyentirely positive, the catheter tip is considered to be located abovethe sinoatrial node, for example in the superior vena cava. If theP-wave includes positive energy and a relatively small amount ofnegative energy, but the positive energy is smaller relative to theR-wave energy, such as is seen at (2260) in FIG. 18D, the catheter tipmay be located at the caval atrial junction. If the P-wave segmentincludes a large amount of negative energy relative to its positiveenergy, and the positive energy is comparable to that of the R-waveenergy, such as is seen in at (2265) in FIG. 18E, the catheter tip maybe in the right atrium. If the P-wave includes substantially entirelynegative energy, as seen at (2270) in FIG. 18F, the catheter tip isapproaching the inferior vena cava or is in the inferior vena cava. Inthis way, the directional energy introduced herein is used by thepresent method described herein for catheter navigation and tiplocation.

FIGS. 22A-22D and 23A-23B illustrate various details regarding aconnector according to example embodiments, which allow for the use ofthe apparatus and method described herein by a single operator in thesterile field.

In particular, FIG. 22A shows a connecting object (2915) includingmagnetic attraction properties and a surface including electricallyconductive properties. The connecting object (2915) electricallyconnects to two connectors (2910) and (2920). The connector (2910) isconnected to one end of a sterile device/adaptor (2905). The other endof the sterile device (2905) can be connected to a sterile guidewire orstylet or to a sterile saline adaptor as described further above. Theconnector (2920) can be attached to or be itself one end of an ECG cableconnected to the apparatus illustrated herein in FIG. 1A.

The surface of the connecting object (2915) can be implemented inseveral ways. In one embodiment, a magnet is built into an enclosurewith an electrical conductive surface. The magnet attracts theelectrical connectors (2910) and (2920) to the metallic surface andlocks them on the surface, thus establishing electrical contact betweenconnector (2910) and the electrically conductive surface of theconnecting object (2915) and another electrical contact between theelectrically conductive surface of the connecting object (2915) and theother electrical contact (2920).

The connecting object 2915 illustrates one type of connector that can beused with the methods described herein by a single operator in thesterile field. Accordingly, in one embodiment, the object (2915) isplaced prior to the commencement of a catheter placement procedure inthe non-sterile field such that it can be reached by the single sterileoperator during the procedure. Then, the as-yet non-sterile operatorconnects one end of the non-sterile connector (2920) to an ECG cable and“drops” the connector end shown in FIG. 22A onto the surface of theconnecting object 2915. Because of the magnet incorporated in the object(2915), the connector (2920) is attracted to the electrically conductivesurface of the connecting object and adheres to the surface thereof. Theend of the ECG cable to which the connector (2920) is attached orincluded can be an ECG lead itself, thus simplifying the workflow.

During the procedure, the single operator is sterile. The operatorsopens the sterile package in which the connector (adaptor) (2910, 2905)is packaged, holds the sterile connector end (2915) with a sterilegloved hand and drops the sterile connector onto the electricallyconductive surface of the connecting object (2915). Similarly toconnector (2920), the connector (2910) is magnetically attracted to theconnecting object (915) by the built-in magnet, which secures theconnector (2910) on the electrically conductive surface of theconnecting object. Using this method, an electrical connection can beestablished between a sterile electrical connector (2910) and anon-sterile connector (2920) without compromising the sterile field.Again, this method can be used by a single operator and enables thesingle sterile operator use of the apparatus described herein.

FIG. 22B illustrates another embodiment of the connector, wherein theconnecting object (2930) is directly connected to a wire or is anintegral part of an ECG cable (2935). This embodiment simplifies themethod described above in connection with FIG. 22A, as only the sterileconnector (2925) connected to the sterile adaptor (2905) must be droppedon to the electrically conductive surface (2930) of the connectingobject (2930) during the sterile procedure.

FIG. 22C illustrates another embodiment of the connecting object,wherein a connector (2940) of the sterile adaptor (2905) is similar tothe adapter (2905) and connector (2910) described above in connectionwith FIG. 22A. During a catheter placement procedure, the sterileoperator drops the sterile connector (2940) into a connecting object, ormating piece (2945). The mating piece (2945) includes a cup thatreceives therein the connector (2940). A magnet is built into the cup,which attracts the connector (2940) into the cup to secure it therein.At the same time, the cup ensures electrical connectivity. The matingpiece (2945) can be an integral part of an ECG cable (2950) (e.g., oneend of an ECG lead), one end of a wire for connection to an ECG cable,or some other suitable configuration. The method for using the matingpiece 2945 is similar to that described in connection with FIG. 22B,with a difference being that the cup (2945) has the ability to suck inthe connector (2940) for a relatively secure male/female-typeconnection. As is the case with the embodiments described in connectionwith FIGS. 22A, 22B, and 22D, the shapes and materials used for theconnecting objects can vary while still ensuring proper electricalcontact for the component interconnected therewith.

FIG. 22D illustrates a connecting object configuration similar to thatdescribed in connection with FIG. 22C, except that a cup (2960), whichcontains a magnet for operably connecting with a connector (2955),includes on an opposite end a connector (2965) to which an ECG cableclip can be attached. As such, during a placement procedure anon-sterile operator can connects the connector (2965) to a commerciallyavailable ECG cable by using the clip provided with the ECG cable.Later, during the sterile procedure, the sterile operator drops thesterile connector (2955) into the cup (2960), similar to the methoddescribed in connection with FIG. 22C.

FIG. 23A illustrates details of a steerable sterile adaptor (3010)according to one embodiment, including a reinforced sterile connectorpiece (3020) of rigid plastic, for instance. Instead of dropping thesterile connector piece (3020) into a mating piece (3030) as in FIGS.22C and 22D, the sterile operator can use the rigid connector piece(3020) of the sterile adaptor (3010) to steer, e.g., push, rotate, etc.,it into the mating piece. In one embodiment, the mating piece (3030)includes a built-in magnet to attract the connector piece 3020. Inanother embodiment, the mating piece (3030) includes no magnet, but isof an appropriate size and shape for the connector piece (3020) to fittherein so as to establish suitable electrical contact therebetween.

FIG. 23B illustrates a steerable connector piece (3040) according to oneembodiment, which can be pushed into and operably connect with a simplemating piece (3050) without the need of a magnet. In addition to whathas been shown and described, other shapes are possible for theconnector (3040) and its mating piece (3050), e.g. rails or screws.

It is appreciated that any suitable combination of the connectorembodiments discussed above can be used. For example, the steerableconnector of FIG. 23B can include a mating piece like that shown in FIG.22D.

FIGS. 24A-24F illustrate various details of catheter navigationaccording to one embodiment. As shown, each of these figures includestwo display windows: a first window showing ECG waveforms, and a secondwindow showing a representation, or icon, of a heart and an additionallocation icon indicating the point of measurement of the ECG signal towhich the ECG waveforms in the first window correspond. The mappingbetween ECG waveforms and the location icon is performed in oneembodiment using the algorithms and methods described above. The twodisplay windows can be used independently or together. In oneembodiment, the two display windows are shown simultaneously on thegraphical user interface (FIG. 1A) in order to allow the operator tocorrelate the observed ECG waveform(s) with catheter tip location. Inanother embodiment, only the heart and location icon window is shown inorder to simplify the user interface.

The location icon can include any one or more of several possibleconfigurations, including an arrow to show advancement in a certaindirection, a dot, a cross, a star, etc., to show an identifiablelocation. Each of these icons can include different colors to emphasizelocation relevance. In another embodiment, different sounds can beassociated to each of the identifiable tip locations. Sounds and iconsidentifying tip locations can be used together or independently to helpthe user navigate the catheter and locate the tip within the patientvasculature.

In one embodiment a simplified user interface is employed, wherein onlythe heart icon and the corresponding location icon(s) are displayed. Inthis instance, the ECG waveforms and the computation behind the locationmapping are not visible to the user. Thus, the apparatus describedherein can be employed for navigation and tip location without requiringuser interpretation of the ECG waveforms. The simplified user interfacewith only the heart and catheter tip location icons can be used as shownin the embodiment illustrated in FIG. 25B, for instance.

In greater detail, FIG. 24A illustrates ECG waveforms corresponding tocatheter tip locations outside the thoracic cavity in the upper body: askin reference ECG Lead III (3110) and an endovascular catheternavigation ECG Lead II (3115). In the icon display window, a heart icon(3125) is displayed and a location icon (3120) shows that the catheteris moving towards the thoracic cavity. In another embodiment, thearrow-shaped location icon (3120) can be replaced with a cross, a dot,or any other suitable icon showing location above and outside thesuperior vena cava.

The arrow-shaped location icon (3120) is displayed by the apparatusaccording to one embodiment only if the algorithms detect changes in thenavigation ECG Lead II that support the fact that the catheter tip ismoving towards the heart, e.g., a steady increase in the electricalenergy and a P-wave with positive directional energy, indicating thatthe tip is approaching the sino-atrial node. If the algorithms do notdetect a steady increase in the electrical energy of the endovascularECG signal as the catheter advances through the vasculature, only a dot,star, cross or other suitable location icon is displayed at a locationabove and outside the superior vena cava. Sounds associated with each ofthese locations and situations can be played in addition to or insteadof the graphical icons.

FIG. 24B illustrates the ECG waveforms corresponding to the referencelead (3110) and catheter navigation lead (3115) at a locationcorresponding to the upper superior vena cava. The icon display windowshows the heart icon (3125) and a dot-shaped location icon (3130)indicating the upper superior vena cava on the heart icon. This locationis determined by the apparatus, as described further above, based on theECG waveforms (3110) and (3115). As in FIG. 24A, any suitable icon shapeand color can be used, and/or a sound or tune can be played when the tipof the catheter reaches the location indicated by the detected ECGwaveforms.

FIG. 24C illustrates the ECG waveforms corresponding to the referencelead (3110) and catheter navigation lead (3115) at a locationcorresponding to the lower third of the superior vena cava. The icondisplay window shows the heart icon (3125) and a dot-shaped locationicon (3140) indicating the lower third of superior vena cava on theheart icon. This location is computed by the apparatus, as describedfurther above, based on the ECG waveforms (3110) and (3115). As in FIG.24A, any suitable icon shape and color can be used and/or a sound ortune can be played when the tip of the catheter reaches the location asindicated by the detected ECG waveforms.

FIG. 24D illustrates the ECG waveforms corresponding to the referencelead (3110) and catheter navigation lead (3115) at a locationcorresponding to the caval-atrial junction. The icon display windowshows the heart icon (3125) and a dot-shaped location icon (3150)indicating the caval-atrial junction on the heart icon. This location iscomputed by the apparatus, as described further above, based on the ECGwaveforms (3110) and (3115). As in FIG. 24A, any suitable icon shape andcolor can be used and/or a sound or tune can be played when the tip ofthe catheter reaches this location as indicated by the detected ECGwaveforms.

FIG. 24E illustrates the ECG waveforms corresponding to the referencelead (3110) and catheter navigation lead (3115) at a locationcorresponding to the right atrium. The icon display window shows theheart icon (3125) and a dot-shaped location icon (3160) indicating theright atrium on the heart icon. This location is computed by theapparatus, as described further above, based on the ECG waveforms (3110)and (3115). As in FIG. 24A, any suitable icon shape and color can beused and/or a sound or tune can be played when the tip of the catheterreaches this location as indicated by the detected ECG waveforms.

FIG. 24F illustrates ECG waveforms corresponding to catheter tiplocations outside the thoracic cavity in the lower body: the skinreference ECG Lead III (3110) and the endovascular catheter navigationECG Lead II (3115). In the icon display window, the heart icon isdisplayed (3125) and an arrow-shaped location icon (3170) showing thatthe catheter is moving away from the thoracic cavity, such as toward theinferior vena cava. In another embodiment, the arrow-shaped locationicon (3170) can be replaced with a cross, a dot, or any other suitableicon showing location below the right atrium.

The arrow-shaped location icon (3170) is displayed by the apparatus inone embodiment only if the algorithms detect changes in the navigationECG Lead II that support the fact that the catheter tip is moving awayfrom the heart, e.g., a steady decrease in the electrical energy and aP-wave with negative directional energy, indicating that the tip ismoving away from the sino-atrial node. If the algorithms do not detect asteady decrease in the electrical energy of the endovascular ECG signalas the catheter advances through the vasculature but detect a negativeP-wave, only a dot, star, cross or any other location icon is displayedat a location below and outside the right atrium. The sounds associatedwith each of these locations and situations can be played in addition toor instead the graphical icons.

FIG. 25A illustrates a display window on a graphical user interface of amobile phone (3210), tablet PC, or other suitable handheld or portabledevice. In particular, the user interface of the mobile phone is showndisplaying waveforms (3220) of two ECG leads: the reference lead and thecatheter navigation lead. The mobile phone or other suitable device isin held in one embodiment in a horizontal position as to allow for alonger time (more heart cycles) of the ECG waveform to be displayed. Ifthe display device is in a real-time display mode, the display switchesautomatically to showing the ECG waveforms each time the device isturned horizontally. In another embodiment only one ECG lead isdisplayed at a time. In yet another embodiment, three or more leads canbe displayed simultaneously. As described in an embodiment of thepresent invention, in another embodiment the screen of the displaydevice can be split in real-time to depict a (current location) displaywindow and a frozen (reference location) window to allow for easierassessment of ECG waveform changes. Two-way interaction between theapparatus shown in FIG. 1A and the mobile phone (3210) to enable thefunctionality shown and described in connection with FIGS. 25A-27B canbe achieved in one embodiment via the wireless connectivity component150, shown in FIG. 1A. It is appreciated that the mobile phone (3210) isequipped with corresponding wireless connectivity so as to enablecommunication therebetween, as appreciated by one skilled in the art.

FIG. 25B illustrates a simplified user interface (3230) displayed on thescreen of a mobile phone (3210) or other suitable handheld/portabledevice based on the navigation interface described in FIGS. 24A-24F.When in real-time display mode and if the display device is positionedvertically, the device automatically displays the simplified userinterface shown in FIG. 25B. When in real-time display mode, the deviceautomatically switches back and forth between displaying ECG waveformswhen the device is held horizontally, illustrated in FIG. 25A, anddisplaying the navigation user interface, illustrated in FIG. 25B whenthe device is held vertically.

FIG. 26 illustrates, in one embodiment, the zoom and scroll functions onthe touch screen of a mobile phone (3310), tablet PC or similar device.The user can use two fingers (3320) to zoom in and out the ECG waveformsfor better visualization. Scrolling through the ECG waveform recordingcan be also achieved using the fingers and the touch screen.

FIG. 27A illustrates the ability, in one embodiment to use a mobilephone (3410), tablet PC, or other suitable handheld/portable device tocommunicate the ECG waveforms and/or the simplified user interface andpatient data to another computer or device. The communication interfaceis illustrated by (3420). Such transfer can be performed by the mobilephone (3410) via a Wi-Fi, cell phone, or other suitable network.

FIG. 27B illustrates the graphical user interface of a mobile phone(3410), tablet PC, or other suitable handheld/portable device, whichallows for the display of patient data (3430), ECG waveforms (3440) or asimplified heart icon depending on the device orientation, and aninterface (3450) browsing, control, and disposition of one or morepatient records, including deleting, copying to memory, etc.

It is appreciated that the apparatus, algorithms, and methods describedherein can be practiced in connection with a variety of environments andusing a variety of components and systems. One example of an ECGmonitoring system with which embodiments of the present invention can bepracticed can be found in U.S. Pat. No. 8,849,382, filed Sep. 10, 2009,and entitled “Apparatus and Display Methods Relating to IntravascularPlacement of a Catheter.” Another example of an ECG monitoring systemcan be found in U.S. Pat. No. 8,388,546, filed Apr. 21, 2009, andentitled “Method of Locating the Tip of a Central Venous Catheter.” Eachof the foregoing applications is incorporated herein by reference in itsentirety.

Non-limiting examples of ECG sensor stylets that can be used inconnection with embodiments of the present invention can be found inU.S. Pat. No. 9,901,714, filed Aug. 21, 2009, and entitled “CatheterAssembly Including ECG Sensor and Magnetic Assemblies,” and U.S. Pat.No. 9,636,031, filed Sep. 29, 2010, and entitled “Stylets for use withApparatus for Intravascular Placement of a Catheter,” each of which isincorporated herein by reference in its entirety.

Embodiments of the invention may be embodied in other specific formswithout departing from the spirit of the present disclosure. Thedescribed embodiments are to be considered in all respects only asillustrative, not restrictive. The scope of the embodiments is,therefore, indicated by the appended claims rather than by the foregoingdescription. All changes that come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

What is claimed is:
 1. A method for locating an indwelling medicaldevice within a body of a patient, the method comprising: detecting aP-wave of an ECG waveform via an electrode associated with theindwelling medical device, the electrode sensing an endovascular ECGsignal via a conductive path into the body of the patient; calculatingat least one of an amount of positive amplitude of the P-wave and anamount of negative amplitude of the P-wave; and determining a positionof a portion of the indwelling medical device based on the calculatedamount of at least one of the positive amplitude and the negativeamplitude of the P-wave, wherein the portion of the indwelling medicaldevice is determined to be above and moving toward a sinoatrial node ofa heart of the patient when the calculated amount of amplitude of theP-wave is positive and is increasing in positive amplitude, whereindetecting the P-wave, calculating at least one of the amounts ofpositive amplitude and negative amplitude, and determining the positionare iteratively performed to determine a change in the amount of atleast one of the positive amplitude and negative amplitude of the P-waveover time.
 2. The method for locating according to claim 1, furthercomprising depicting the determined position of the portion of theindwelling medical device on a display.
 3. The method for locatingaccording to claim 1, further comprising depicting the detected P-waveof the ECG signal on a display.
 4. The method for locating according toclaim 1, wherein the amount of positive amplitude includes an amount ofP-wave amplitude above a baseline of the ECG waveform and wherein theamount of negative amplitude includes an amount of P-wave amplitudebelow the baseline of the ECG waveform.
 5. The method for locatingaccording to claim 1, wherein determining the position of the portion ofthe indwelling medical device further includes determining the portionof the indwelling medical device to be below and moving away from thesinoatrial node when the amplitude of the P-wave is negative and isincreasing in negative amplitude.
 6. The method for locating accordingto claim 1, wherein at least one of detecting the P-wave, calculating atleast one of the amounts, and determining the position is at leastpartially controlled or monitored by a mobile phone or handheld device.